Publications by authors named "Wenjing Gao"

66 Publications

The Roles of Genetic and Early-Life Environmental Factors in the Association Between Overweight or Obesity and Hypertension: A Population-Based Twin Study.

Front Endocrinol (Lausanne) 2021 5;12:743962. Epub 2021 Oct 5.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

Aims/hypothesis: We aimed to explore whether and to what extent overweight or obesity could increase the risk of hypertension, and further to estimate the roles of genetic and early-life familial environmental factors in their association.

Methods: This prospective twin study was based on the Chinese National Twin Registry (CNTR), which collected information from self-report questionnaires. We conducted unmatched case-control analysis to examine the association between overweight or obesity and hypertension. And further to explore whether genetics and familiar environments shared within a twin pair, accounted for their association co-twin matched case-control design. Generalized estimating equation (GEE) models and conditional logistic regressions were used in the unmatched and matched analyses, respectively. Then, we used logistic regressions to test the difference in odds ratios (ORs) between the unmatched and matched analyses. Finally, through bivariate twin model, the roles of genetic and environmental factors in the body mass index (BMI)- hypertension association were estimated.

Results: Overall, we included a total of 30,617 twin individuals, of which 7533 (24.6%) twin participants were overweight or obesity and 757 (2.5%) developed hypertension during a median follow-up time of 4.4 years. In the GEE model, overweight or obesity was associated with a 94% increased risk of hypertension (OR=1.94, 95% confidence interval (CI): 1.64~2.30). In the conditional logistic regression, the multi-adjusted OR was 1.80 (95% CI: 1.18~2.74). The difference in OR between unmatched and matched analyses was significant (=0.016). Specifically, overweight or obesity was not associated with hypertension risk in the co-twin design when we full controlled genetic and familiar environmental factors (OR=0.89, 95 CI: 0.46~1.72). After controlling for age and sex, we found the positive BMI-hypertension association was mainly explained by a genetic correlation between them ( = 0.59, 95% CI: 0.44~1.00).

Conclusions/interpretation: Genetics and early-life environments shared by participants within a twin pair appear to account for the association between overweight or obesity and hypertension risk.
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http://dx.doi.org/10.3389/fendo.2021.743962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525506PMC
October 2021

Diagnostic performance of elastography for breast non-mass lesions: A systematic review and meta-analysis.

Eur J Radiol 2021 Oct 2;144:109991. Epub 2021 Oct 2.

Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China. Electronic address:

Purpose: This systematic review and meta-analysis aimed to evaluate the diagnostic performance of ultrasound elastography in the differentiation of benign and malignant breast non-mass lesions (NMLs).

Methods: PubMed, Cochrane Library, and Embase databases were searched for eligible studies up to end of June 2021. The diagnostic performance of elastography for NMLs was investigated using pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio (DOR), post-test probability, and the area under hierarchical summary receiver operating characteristic curve (HSROC).

Results: Eleven studies involving 812 NMLs (malignant 414) were included. The pooled sensitivity, specificity, DOR, positive likelihood ratio, and negative likelihood of elastography for the differentiation of benign and malignant breast NMLs were 79% (95 %CI: 71-85), 86% (95 %CI: 79-91), 23.32 (95 %CI: 13.38-40.66), 5.67 (95 %CI: 3.79-8.47), and 0.24 (95 %CI: 0.17-0.34), respectively. No significant publication bias existed. The area under the HSROC curve was 90% (95 %CI: 87-92). Fagan plots demonstrated good clinical utility. However, substantial heterogeneity existed. Country, measurement index, and number of lesions served as potential sources of heterogeneity.

Conclusions: The results of this study suggest that elastography has high diagnostic accuracy in differentiating between malignant and benign NMLs. Elastography can be a feasible and non-invasive tool for breast NMLs.
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http://dx.doi.org/10.1016/j.ejrad.2021.109991DOI Listing
October 2021

A Comparison of Preterm Birth Rate and Growth from Birth to 18 Years Old between in Vitro Fertilization and Spontaneous Conception of Twins.

Twin Res Hum Genet 2021 Aug 20;24(4):228-233. Epub 2021 Sep 20.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1-2 years), preschool (3-5 years), primary or elementary school (6-11 years), and adolescence (10-18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0-18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
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http://dx.doi.org/10.1017/thg.2021.33DOI Listing
August 2021

Overweight and Risk of Type 2 Diabetes: A Prospective Chinese Twin Study.

Diabetes Metab 2021 Sep 11:101278. Epub 2021 Sep 11.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

Objectives: This study aimed to estimate the association between overweight and type 2 diabetes mellitus (T2DMM) in twins, and further to explore whether genetic and early-life environmental factors account for this association.

Methods: This study included 31,197 twin individuals from the Chinese National Twin Registry (CNTR). Generalised estimating equation (GEE) models were applied for unmatched case-control analysis. Conditional logistic regressions were used in co-twin matched case-control analysis. Logistic regressions were fitted to examine the differences in odds ratios (ORs) from the GEE models and conditional logistic regressions. Bivariate genetic model was used to explore the genetic and environmental correlation between body mass index (BMI) and T2DM.

Results: In the GEE model, overweight was associated with a higher T2DM risk (OR=2.71, 95% confidence interval (CI): 1.96∼3.73), compared with participants with normal BMI. In the multi-adjusted conditional logistic regression, the association was still significant (OR=2.60, 95% CI: 1.15∼5.87). The ORs from the unmatched and matched analyses were different (P = 0.042). Particularly, overweight could increase T2DM risk in monozygotic (MZ) twins, and the difference in ORs between the unmatched and matched designs was significant (P = 0.014). After controlling for age and sex, the positive BMI-T2DM association was partly due to a significant genetic correlation (rA= 0.31, 95% CI: 0.20∼0.41).

Conclusions: Our findings suggest that genetics and early-life environments might account for the observed overweight-T2DM association. Genetic correlation between BMI and T2DM further provides evidence for the influence of overlap genes on their association.
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http://dx.doi.org/10.1016/j.diabet.2021.101278DOI Listing
September 2021

Cross-neutralization of RBD mutant strains of SARS-CoV-2 by convalescent patient derived antibodies.

Biotechnol J 2021 Aug 11:e2100207. Epub 2021 Aug 11.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.

Background: The emergence of COVID-19 pandemic resulted in an urgent need for the development of therapeutic interventions. Of which, neutralizing antibodies play a crucial role in the prevention and resolution of viral infection.

Methods: We generated antibody libraries from 18 different COVID-19 recovered patients and screened neutralizing antibodies to SARS-CoV-2 and its mutants. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Clones were then reconstituted into whole human IgG for epitope binning assay and all 19 IgG were classified into 6 different epitope groups or Bins.

Results: Although all antibodies were found to bind RBD, the antibodies in Bin2 had superior inhibitory ability of the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 showed stronger binding affinity or ability to mutant RBDs (N501Y, W463R, R408I, N354D, V367F, and N354D/D364Y) derived from different SARS-CoV-2 strains as well, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 and its mutations. Furthermore, such neutralizing antibodies strongly restricted the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized wildtype and more transmissible mutant pseudovirus entry into hACE2 overexpressed 293T cells. In Vero-E6 cells, one of these antibodies can even block the entry of live SARS-CoV-2 into cells at 12.5 nM.

Conclusions: These results indicate that the neutralizing human antibodies from the patient-derived antibody libraries have the potential to fight SARS-CoV-2 and its mutants in this global pandemic.
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http://dx.doi.org/10.1002/biot.202100207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420279PMC
August 2021

Combined healthy lifestyle score and risk of epigenetic aging: a discordant monozygotic twin study.

Aging (Albany NY) 2021 05 25;13(10):14039-14052. Epub 2021 May 25.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China.

We investigated whether lifestyle influences epigenetic aging in 143 monozygotic twin pairs discordant for the combined healthy lifestyle score. Twins were scored for four lifestyle factors as unhealthy or healthy; non-smoker, moderate drinker, adequate fruit and vegetable intake, and sufficient physical activity. The combined healthy lifestyle score was calculated for each participant by summing the binary score for each factor. Individual and co-twin analyses were used to assess the relationship between single or combined lifestyle scores, along with DNA methylation age acceleration (AA) calculated using Horvath's and Li's epigenetic clocks, focusing on AA and intrinsic epigenetic age acceleration (IEAA) measures. Compared with the twins that scored no or one healthy lifestyle point, those who scored four healthy lifestyle points had lower Li_IEAA with similar results observed in the co-twin analysis. No significant relationships were found in analyses based on Horvath's clock, although the direction of correlations was consistent with that determined using Li's clock. Smoking and drinking did not significantly affect DNA methylation AA; however, physical activity and intake of vegetables and fruits did, although the influence varied depending on the epigenetic clock. Our findings suggest that a healthy lifestyle may be an important way to delay aging and prevent age-related diseases.
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http://dx.doi.org/10.18632/aging.203022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202852PMC
May 2021

Application of MALDI-TOF MS Profiling Coupled With Functionalized Magnetic Enrichment for Rapid Identification of Pathogens in a Patient With Open Fracture.

Front Chem 2021 30;9:672744. Epub 2021 Apr 30.

Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province, Institute of Mass Spectrometry, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, China.

Posttraumatic infections can occur in orthopedic trauma patients, especially in open fractures. Rapid and accurate identification of pathogens in orthopedic trauma is important for clinical diagnosis and antimicrobial treatment. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been successfully used for first-line identification of pathogens grown on culture plates. However, for direct analysis of liquid clinical specimens, pre-purification of the sample is necessary. Herein, we investigated the feasibility of coupling [email protected] enrichment with MALDI-TOF MS profiling in the identification of pathogens in liquid-cultured samples. This method is successfully used for the identification of pathogens in a patient with an open-leg fracture obtained at sea. Pathogens were enriched by [email protected] from briefly pre-cultured liquid media and identified by MALDI-TOF MS. We identified an opportunistic pathogen, , which is uncommon in clinical orthopedic trauma infection but exists widely in the sea. Therefore, combining [email protected] enrichment and MALDI-TOF MS profiling has great potential for direct identification of microbes in clinical samples.
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http://dx.doi.org/10.3389/fchem.2021.672744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120279PMC
April 2021

Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study.

Epigenomics 2021 Jun 17;13(12):939-951. Epub 2021 May 17.

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing 100191, PR China.

Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. The hypermethylation of cg07326074, located in the tumor-promoting gene , was associated with alcohol consumption.
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http://dx.doi.org/10.2217/epi-2021-0039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147754PMC
June 2021

Associations of Obesity Measurements with Serum Metabolomic Profile: A Chinese Twin Study.

Twin Res Hum Genet 2021 02;24(1):14-21

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

The objective of this study was to investigate how different obesity measures link to circulating metabolites, and whether the connections are due to genetic or environmental factors. A cross-sectional analysis was performed on follow-up survey data at the Chinese National Twin Registry (CNTR), which was conducted in four areas of China (Shandong, Jiangsu, Zhejiang and Sichuan) in 2013. The survey collected detailed questionnaire information and conducted physical examinations, fasting blood sampling and untargeted metabolomic measurements among 439 adult twins. Linear regression models and bioinformatics analysis were used to examine the relation of obesity measures, including body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) with serum metabolite levels and related pathways. A co-twin control study was additionally conducted among 15 obesity-discordant monozygotic (MZ) pairs (intrapair BMI difference >3 kg/m2) to examine any differences in metabolites controlling for genetic factors. Eleven metabolites were associated with BMI, WC and WHR after controlling for genetic and shared environmental factors. Pathway analysis identified pathways such as phenylalanine metabolism, purine metabolism, valine, leucine and isoleucine biosynthesis that were associated with obesity. A wide range of unfavorable alterations in the serum metabolome was associated with obesity. Obesity-discordant twin analysis suggests that these associations are independent of genetic liability.
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http://dx.doi.org/10.1017/thg.2021.3DOI Listing
February 2021

Associations of Metabolic/Obesity Phenotypes with Insulin Resistance and C-Reactive Protein: Results from the CNTR Study.

Diabetes Metab Syndr Obes 2021 15;14:1141-1151. Epub 2021 Mar 15.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, People's Republic of China.

Background: Obesity is a heterogeneous condition in terms of metabolic status. Different obesity phenotypes have various health risks. The aim of this work was to define different subtypes of obesity and investigate their relationship with inflammatory-cardiometabolic abnormalities among Chinese adult twins.

Methods: The analyses used data from 1113 adult twins in 4 provinces (Shandong, Zhejiang, Jiangsu and Sichuan) from Chinese National Twin Registry (CNTR) which collected detailed information. We defined those with 0 or 1 metabolic syndrome (MetS) components excluding waist circumference as metabolically healthy, and those with waist circumference ≥90 cm (for men) and ≥85 cm (for women) as obese. The two-category obesity status and metabolic states are combined to generate four metabolic/obesity phenotypes. High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as surrogate measure of insulin resistance. Mixed-effect linear regression models and fixed-effect linear regression models were used to analyse the correlation between HOMA-IR, hsCRP and different metabolic/obesity phenotypes.

Results: In cross-sectional analyses of 1113 individuals (mean [SD] age, 46.6 [12.9] years; 463 obese [41.6%]), 20.3% obese twins were metabolic healthy and 64.2% non-obese twins were metabolic unhealthy. Serum HOMA-IR level was higher in metabolically unhealthy non-obesity (MUNO) (β=0.42, 95% CI: 0.21-0.64), metabolically healthy obesity (MHO) (β=0.68, 95% CI: 0.36-1.00) and metabolically unhealthy obesity (MUO) (β=0.69, 95% CI: 0.46-0.91) twins, compared with their metabolically healthy non-obesity (MHNO) counterparts. HsCRP was similar between MHO and MUO, which differed significantly to metabolic healthy non-obesity (MHNO).

Conclusion: MHO and MUNO phenotypes were common in Chinese twin population. Both phenotypes were associated with elevated IR and hsCRP which may not be benign and need to be concerned.
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http://dx.doi.org/10.2147/DMSO.S298499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979357PMC
March 2021

Antibody seroprevalence in the epicenter Wuhan, Hubei, and six selected provinces after containment of the first epidemic wave of COVID-19 in China.

Lancet Reg Health West Pac 2021 Mar 5;8:100094. Epub 2021 Feb 5.

National Institute for Viral Disease Control and Prevention (China CDC), Beijing, China.

Background: China implemented containment measures to stop SARS-CoV-2 transmission in response to the COVID-19 epidemic. After the first epidemic wave, we conducted population-based serological surveys to determine extent of infection, risk factors for infection, and neutralization antibody levels to assess the real infections in the random sampled population.

Methods: We used a multistage, stratified cluster random sampling strategy to conduct serological surveys in three areas - Wuhan, Hubei Province outside Wuhan, and six provinces selected on COVID-19 incidence and containment strategy. Participants were consenting individuals >1 year old who resided in the survey area >14 days during the epidemic. Provinces screened sera for SARS-CoV-2-specific IgM, IgG, and total antibody by two lateral flow immunoassays and one magnetic chemiluminescence enzyme immunoassay; positive samples were verified by micro-neutralization assay.

Findings: We enrolled 34,857 participants (overall response rate, 92%); 427 were positive by micro-neutralization assay. Wuhan had the highest weighted seroprevalence (4•43%, 95% confidence interval [95%CI]=3•48%-5•62%), followed by Hubei-ex-Wuhan (0•44%, 95%CI=0•26%-0•76%), and the other provinces (<0•1%). Living in Wuhan (adjusted odds ratio aOR=13•70, 95%CI= 7•91-23•75), contact with COVID-19 patients (aOR=7•35, 95%CI=5•05-10•69), and age over 40 (aOR=1•36, 95%CI=1•07-1•72) were significantly associated with SARS-CoV-2 infection. Among seropositives, 101 (24%) reported symptoms and had higher geometric mean neutralizing antibody titers than among the 326 (76%) without symptoms (30±2•4 vs 15±2•1, <0•001).

Interpretation: The low overall extent of infection and steep gradient of seropositivity from Wuhan to the outer provinces provide evidence supporting the success of containment of the first wave of COVID-19 in China. SARS-CoV-2 infection was largely asymptomatic, emphasizing the importance of active case finding and physical distancing. Virtually the entire population of China remains susceptible to SARS-CoV-2; vaccination will be needed for long-term protection.

Funding: This study was supported by the Ministry of Science and Technology (2020YFC0846900) and the National Natural Science Foundation of China (82041026, 82041027, 82041028, 82041029, 82041030, 82041032, 82041033).
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http://dx.doi.org/10.1016/j.lanwpc.2021.100094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864613PMC
March 2021

Ameliorative and protective effects of fucoidan and sodium alginate against lead-induced oxidative stress in Sprague Dawley rats.

Int J Biol Macromol 2020 Apr 27;158:662-669. Epub 2020 Apr 27.

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.

The current study was performed to evaluate the possible protective effects of fucoidan (F) and sodium alginate (SA) against lead-induced oxidative damage in vivo, and to identify relevant underlying mechanisms. Health Sprague Dawley (SD) rats were divided into nine groups of ten rats each and treated orally with lead acetate (5 mg/kg, Pb) for 4 weeks, then gavaged with DMSA (Meso-2, 3-dimercaptosuccinic acid, 25 mg/kg), F (50, 100, 200 mg/kg) and SA (50, 100, 200 mg/kg) individually after successful modelling. We found that the administration of both F or SA resulted in a beneficial effect by significantly decreasing lead levels (p < 0.05) in the kidneys from 2.85 mg/kg to 0.79 mg/kg and improving antioxidant status (SOD, GSH, and CAT) thereby alleviating lead-induced damage and injury of the liver and kidneys (AST, BUN, and Cr). Both natural extracts exerted dose-dependent effects. Protective effects were further demonstrated by histopathology. Our results demonstrate that the F and SA are effective natural extracts for lead-eliminating, and that they can ameliorate oxidative damage induced by lead toxicity.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.04.192DOI Listing
April 2020

The Paradox Association between Smoking and Blood Pressure among Half Million Chinese People.

Int J Environ Res Public Health 2020 04 20;17(8). Epub 2020 Apr 20.

Environmental Research Center, Duke Kunshan University, Kunshan 215316, China.

: The association between smoking and blood pressure (BP) has been explored extensively, yet the results remain inconclusive. Using real-world evidence of a large Chinese population, we examine the effect of smoking on BP levels. : We utilize half a million adults from the China Kadoorie Biobank (CKB) study with baseline sampling collected between 2004 and 2008. Multivariable linear regression analyses are used to estimate linear regression coefficients of smoking for systolic blood pressure (SBP) and diastolic blood pressure (DBP). 459,815 participants (180,236 males and 279,579 females) are included in the analysis. Regular smoking is significantly associated with lower SBP (-0.57 mm Hg, < 0.001) and DBP (-0.35 mm Hg, < 0.001) when compared with non-smoking in men. Additionally, SBP and DBP decrease significantly among all groups of different smoking status in women ( < 0.001). Additionally, pack-years show negative associations with SBP and DBP in both men and women. Further analysis shows the interaction of smoking and alcohol consumption is associated with an increase of SBP and DBP (men: 2.38 mm Hg and 0.89 mm Hg; women: 5.21 mm Hg and 2.62 mm Hg) among co-regular smokers and regular drinkers when compared with regular smokers who are not exposed to alcohol consumption. A negative association between smoking and BP is observed. However, the interaction between smoking and alcohol consumption is associated with BP increase. The findings suggest the importance of considering smoking and alcohol consumption in BP control in addition to antihypertensive treatment in clinical and public health practice.
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http://dx.doi.org/10.3390/ijerph17082824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215755PMC
April 2020

Association between blood pressure levels and cardiovascular deaths: a 20-year follow-up study in rural China.

BMJ Open 2020 02 25;10(2):e035190. Epub 2020 Feb 25.

Epidemiology and Biostatistics, Peking University, Beijing, China.

Objectives: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline recommended 130/80 mm Hg as blood pressure (BP) target goals. However, the generalisability of this recommendation to populations at large with hypertension remains controversial. We assessed the association between BP and cardiovascular diseases (CVDs) mortality using a 20-year follow-up study among Chinese populations.

Design: Prospective cohort study.

Participants: 7314 participants were followed up for a median of 20 years in Fangshan District, Beijing, China.

Methods: The primary outcome variable was death from cardiovascular causes. The adjusted HR for CVDs mortality associated with baseline BP was calculated using Cox regression analysis.

Results: We identified 350 deaths from CVDs (148 stroke, 113 coronary heart disease and 89 other CVDs) during follow-up. Hypertension (defined by systolic BP (SBP)/diastolic BP (DBP) ≥140/90 mm Hg) was significantly associated with mortality due to CVDs (HR=2.49, 95% CI=1.77 to 3.50) among people aged 35-59 years rather than people aged ≥60 years. In addition, there was no significant association between stage 1 hypertension defined by the 2017 ACC/AHA (SBP/DBP of 130-139/80-89 mm Hg) and CVDs mortality when compared with SBP/DBP of <120/80 in neither the participants aged <60 years (HR=0.90, 95% CI=0.54 to 1.50) nor participants aged ≥60 years (HR=1.47, 95% CI=0.94 to 2.29).

Conclusion: The study revealed hypertension of SBP/DBP≥140/90 mm Hg was an important risk factor of CVDs mortality, especially among people aged 35-59 years. However, stage 1 hypertension under the definition of 2017 ACC/AHA was not associated with an increased risk of CVDs mortality. This study indicated that whether adopting the new hypertension definition needs further consideration in rural Chinese populations.
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http://dx.doi.org/10.1136/bmjopen-2019-035190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045167PMC
February 2020

The Chinese National Twin Registry: A Unique Data Source for Systems Epidemiology of Complex Disease.

Twin Res Hum Genet 2019 12 11;22(6):482-485. Epub 2019 Nov 11.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

The Chinese National Twin Registry (CNTR), initiated in 2001, has now become the largest twin registry in Asia. From 2015 to 2018, the CNTR continued to receive Chinese government funding and had recruited 61,566 twin-pairs by 2019 to study twins discordant for specific exposures such as environmental factors, and twins discordant for disease outcomes or measures of morbidity. Omic data, including genetics, genomics, metabolomics, and proteomics, and gut microbiome will be tested. The integration of omics and digital technologies in public health will advance our understanding of precision public health. This review introduces the updates of the CNTR, including study design, sample size, biobank, zygosity assessment, advances in research and future systems epidemiologic research.
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http://dx.doi.org/10.1017/thg.2019.85DOI Listing
December 2019

The GTF2I rs117026326 polymorphism is associated with neuromyelitis optica spectrum disorder but not with multiple sclerosis in a Northern Han Chinese population.

J Neuroimmunol 2019 12 28;337:577045. Epub 2019 Aug 28.

Department of Neurology, The First Hospital of Jilin University, China. Electronic address:

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are common demyelinating disorders of the central nervous system. The etiology and pathogenesis of MS and NMOSD remain unclear. The pathogenesis of these two diseases involves a genetic predisposition as well as environmental factors. NMOSD sometimes co-exists with Sjögren's syndrome, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), and these diseases are frequently associated with central nervous system disorder involvement, as manifest in MS- and NMOSD-like clinical features. Genetic variant rs117026326 upstream of the general transcription factor II-I (GTF2I) has been associated with primary Sjögren's syndrome, SLE and RA in East Asian populations. In this study, we genotyped single nucleotide rs117026326 polymorphisms of the GTF2I gene in 168 patients with MS, 144 patients with NMOSD, and 1403 healthy controls. We observed a significant genetic association between the variant rs117026326 and NMOSD (P = 1.09 × 10, OR = 2.535), however, the association with MS was not significant (P = .4289, OR = 1.129). Gene expression analyses showed that there was no significant association between the messenger RNA expression of GTF2I and genotypes at the variant. We conclude that the risk T allele of rs117026326 increases the risk of NMOSD, suggesting that NMOSD and MS may have different genetic risk factors.
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http://dx.doi.org/10.1016/j.jneuroim.2019.577045DOI Listing
December 2019

Diffusion kurtosis imaging as an imaging biomarker for predicting prognosis of the patients with high-grade gliomas.

Magn Reson Imaging 2019 11 16;63:131-136. Epub 2019 Aug 16.

Department of Radiology, Qilu Hospital of Shandong University, Jinan, China. Electronic address:

Purpose: To retrospectively explore the utilization of MR diffusion kurtosis imaging (DKI) in predicting prognosis of the patients with high-grade gliomas.

Materials And Methods: Thirty-three consecutive patients with cerebral gliomas underwent pretreatment DKI and diffusion-weighted imaging examination on a 3.0-T MR scanner. Diffusion parameters, including conventional tensor parameters, kurtosis metrics (mean kurtosis [MK], radial kurtosis [AK], and axial kurtosis [RK]), and minimum apparent diffusion coefficient (minADC), were obtained and normalized to the contralateral normal-appearing white matter. Correlations among each diffusion parameter and overall survival were analyzed by a Spearman method. The diagnostic efficiency of each parameter in predicting survival for patients with high-grade gliomas was assessed by a receiver operating characteristic curve. The favorable prognostic imaging biomarkers were further analyzed by using a Kaplan-Meier method with log-rank test.

Results: In 33 patients, 17 patients reached overall survival >15 months (long survival group), whereas 16 showed overall survival <15 months (short survival group). Negative correlations between kurtosis metrics (MK, AK, and RK) and overall survival were obtained by using Spearman analysis (r = -0.63, -0.57, and -0.61, respectively, all P < 0.01), whereas minADC was positively correlated with overall survival (r = 0.56, P < 0.01). The kurtosis parameters of the long survival group were significantly lower than that of the short survival group (P < 0.001), while the minADC of the long survival group was significantly higher than that of the short survival group (P = 0.002). Among these diffusion parameters, the optimal cut-off value of MK (0.688) provided the best combination of sensitivity (93.75%) and specificity (76.47%) for differentiation of patients with long survival from those with short survival. High kurtosis metrics and low minADC were significant predictors of poor outcome. (P < 0.05).

Conclusion: Both kurtosis metrics and minADC have the potential to predict survival for the patients with high-grade gliomas. The preoperative kurtosis parameters, especially MK, can be taken as a preoperative prognostic biomarker to predict prognosis in patients with high-grade gliomas.
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http://dx.doi.org/10.1016/j.mri.2019.08.001DOI Listing
November 2019

The tomato WV gene encoding a thioredoxin protein is essential for chloroplast development at low temperature and high light intensity.

BMC Plant Biol 2019 Jun 20;19(1):265. Epub 2019 Jun 20.

Key Laboratory of Horticultural Plant Biology (Ministry of Education), Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Background: Chloroplast biogenesis, a complex process in higher plants, is the key to photoautotrophic growth in plants. White virescent (wv) mutants have been used to unfold the molecular mechanisms underlying the regulation of chloroplast development and chloroplast gene expression in plants. However, most of genes controlling white virescent phenotype still remain unknown.

Results: In this study, we identified a temperature- and light intensity-sensitive mutant, named as wv. The content of chlorophyll was dramatically decreased in the immature leaves of wv mutant under the conditions of low temperature and high-light intensity. TEM observation showed that the chloroplasts in the young leaves of wv mutant lacked an organized thylakoid membrane, whereas crescent-shaped chloroplasts with well-developed stromal and stacked grana thylakoids in the mature leaves were developed. Immunoblot analyses suggested that proteins of photosynthetic complexes were decreased substantially in wv mutants. Based on map-based cloning and transgenic analysis, we determined that the wv phenotype was caused by single base mutation in the first intron of WV gene, which encoded a thioredoxin protein with 365 amino acids. qRT-PCR analysis revealed that the expression of WV gene was significantly down-regulated in wv mutant. In addition, knockdown of WV gene through RNAi also resulted in white virescent young leaves, suggesting that the mutation possibly blocks the differentiation of chloroplasts through inhibiting the expression of WV gene. Furthermore, the expression of WV peaked in apical buds and gradually decreased along with the developmental stage, which was consistent with the wv mutant phenotype. Expression analysis of chloroplast-encoded genes by qRT-PCR showed that the wv mutation affected the expression pattern of chloroplast-encoded PEP dependent genes.

Conclusion: Our results suggested that wv mutant was sensitive to low temperature and light intensity. WV gene was essential for chloroplast differentiation. A single base mutation in the first intron resulted in down-regulation of WV gene expression, which inhibited the expression of chloroplast-encoded genes, thereby blocking chloroplast formation and chlorophyll synthesis.
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http://dx.doi.org/10.1186/s12870-019-1829-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585109PMC
June 2019

On-line Writing of Fiber Bragg Grating Array on a Two-mode Optical Fiber for Sensing Applications.

Materials (Basel) 2019 Apr 17;12(8). Epub 2019 Apr 17.

National Engineering Laboratory for Fiber Optic Sensing Technology, Wuhan University of Technology, Wuhan 430070, China.

On-line fabricated fiber Bragg grating (FBG) array and its sensing potentials have attracted plenty of attention in recent years. In this paper, FBG arrays are written on-line on a two-mode fiber, and this two-mode fiber Bragg grating (TM-FBG) is further experimentally investigated for temperature and curvature sensing. The responses of this sensor were characterized by 11.2 pm/°C and -0.21 dB/m for temperature and curvature, respectively. Based on the measurements, a dual-parameter fiber sensing system was developed, which can realize the quasi-distributed, simultaneous detection of temperature and curvature, making it suitable for structural health monitoring or perimeter security.
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http://dx.doi.org/10.3390/ma12081263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515046PMC
April 2019

Low-density lipoprotein receptor-related protein 1 regulates muscle fiber development in cooperation with related genes to affect meat quality.

Poult Sci 2019 Sep;98(9):3418-3425

College of Animal Science, Jilin University, Changchun 130062, P. R. China.

Low-density lipoprotein receptor-related protein 1 (LRP1) is an important signal protein that is widely involved in physiological processes, such as lipid metabolism, cell movement, and disease processes. However, the relationship between LRP1 and meat quality remains unknown in chickens. The present study aimed to investigate the correlation between LRP1 and meat quality that builds on our preliminary research, as well as to reveal the underlying molecular mechanism of LRP1 on meat-quality traits. The results showed that LRP1 was significantly correlated with shear force (P < 0.05). Several key genes involved in muscle growth and development, including IGF-1, IGFBP-5, IGF-1R, IGF-2, and MyoD, were down-regulated significantly (P < 0.05 or P < 0.01), and MSTN was up-regulated significantly (P < 0.01) in the presence of LRP1 interference. Cell proliferation- or apoptosis-related genes, including PMP22, CDKN2C, and p53, increased significantly (P < 0.05 or P < 0.01), whereas Bcl-x decreased significantly (P < 0.05) in the RNAi group. We conclude that LRP1 regulates muscle fiber development in cooperation with related genes that affect myoblast proliferation and apoptosis, thereby impacting shear force in chickens. This study will provide a valuable resource for biological investigations of muscle growth and meat-quality-related genes in chickens. The results could be useful in identifying candidate genes that could be used for selective breeding to improve meat quality.
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http://dx.doi.org/10.3382/ps/pez168DOI Listing
September 2019

Functional variants of TNFAIP3 are associated with systemic lupus erythematosus in a cohort of Chinese Han population.

Hum Immunol 2019 Feb 5;80(2):140-145. Epub 2018 Dec 5.

The Bethune Institute of Epigenetic Medicine, The First Hospital of Jilin University, Changchun, China. Electronic address:

Tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) is a negative regulator of NF-κB activity. We previously reported that the paired tandem polymorphic dinucleotides TT > A (rs148314165, rs200820567 of TNFAIP3) conferred the risk for systemic lupus erythematosus (SLE) in European and Korean populations. We investigated the genetic association of the TT > A variants, as well as the functional coding variant rs2230926 in exon 3 of TNFAIP3 in 1229 Chinese Han SLE patients and 1608 matched population controls. We further evaluated the role of these variants in regulating expression of the TNFAIP3 gene and NF-κB signaling pathway in their peripheral blood mononuclear cells from Chinese SLE patients. The TT > A variants and the TNFAIP3 exon 3 coding variant rs2230926 demonstrated significant associations in SLE (P = 8.96 × 10, odds ratio [OR] = 2.07, 95% confidence interval [CI] = 1.68-2.55). SLE patients carrying the risk A allele showed reduced messenger RNA expression of the TNFAIP3 gene and increased expression of NF-κB1 in PBMCs. Conditional analyses revealed that the TT > A variants are likely to be causal variants in Chinese Han SLE patients. The TT > A variants associated with Chinese Han SLE and negatively regulate the expression of the TNFAIP3 gene resulting in enhanced NF-κB activity.
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http://dx.doi.org/10.1016/j.humimm.2018.11.008DOI Listing
February 2019

Publisher Correction: A functional variant in the OAS1 gene is associated with Sjögren's syndrome complicated with HBV infection.

Sci Rep 2018 Nov 14;8(1):17031. Epub 2018 Nov 14.

The Bethune Institute of Epigenetic Medicine, The First Hospital of Jilin University, Changchun, China.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-35438-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235960PMC
November 2018

Measuring the lactate-to-creatine ratio via H NMR spectroscopy can be used to noninvasively evaluate apoptosis in glioma cells after X-ray irradiation.

Cell Mol Biol Lett 2018 15;23:27. Epub 2018 Jun 15.

2Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012 China.

Background: Radiotherapy is among the commonly applied treatment options for glioma, which is one of the most common types of primary brain tumor. To evaluate the effect of radiotherapy noninvasively, it is vital for oncologists to monitor the effects of X-ray irradiation on glioma cells. Preliminary research had showed that PKC-ι expression correlates with tumor cell apoptosis induced by X-ray irradiation. It is also believed that the lactate-to-creatine (Lac/Cr) ratio can be used as a biomarker to evaluate apoptosis in glioma cells after X-ray irradiation. In this study, we evaluated the relationships between the Lac/Cr ratio, apoptotic rate, and protein kinase C iota (PKC-ι) expression in glioma cells.

Methods: Cells of the glioma cell lines C6 and U251 were randomly divided into 4 groups, with every group exposed to X-ray irradiation at 0, 1, 5, 10 and 15 Gy. Single cell gel electrophoresis (SCGE) was conducted to evaluate the DNA damage. Flow cytometry was performed to measure the cell cycle blockage and apoptotic rates. Western blot analysis was used to detect the phosphorylated PKC-ι (p-PKC-ι) level. H NMR spectroscopy was employed to determine the Lac/Cr ratio.

Results: The DNA damage increased in a radiation dose-dependent manner ( < 0.05). With the increase in X-ray irradiation, the apoptotic rate also increased (C6,  < 0.01; U251,  < 0.05), and the p-PKC-ι level decreased (C6,  < 0.01; U251,  < 0.05). The p-PKC-ι level negatively correlated with apoptosis, whereas the Lac/Cr ratio positively correlated with the p-PKC-ι level.

Conclusion: The Lac/Cr ratio decreases with an increase in X-ray irradiation and thus can be used as a biomarker to reflect the effects of X-ray irradiation in glioma cells.
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http://dx.doi.org/10.1186/s11658-018-0092-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003206PMC
October 2018

Exposure to Polycyclic Aromatic Hydrocarbons and Accelerated DNA Methylation Aging.

Environ Health Perspect 2018 06 14;126(6):067005. Epub 2018 Jun 14.

Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Background: Aging is related to an increased risk of morbidity and mortality and is affected by environmental factors. Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health outcomes; but the association of such exposure with DNA methylation aging, a novel aging marker, is unclear.

Objectives: Our aim was to investigate the association of PAH exposure with methylation aging.

Methods: We trained and validated a methylation age predictor suitable for Chinese populations using whole blood methylation data in 989 Chinese and 160 Caucasians. We defined two aging indicators: δage, as methylation age minus chronological age; and aging rate, the ratio of methylation to chronological age. The association of PAH exposure with aging indicators was evaluated using linear regressions in three panels of healthy Chinese participants (=539, among the aforementioned 989 Chinese participants) whose exposure levels were assessed by 10 urinary monohydroxy-PAH metabolites.

Results: We developed a methylation age predictor providing accurate predictions in both Chinese individuals and Caucasian persons (R=0.94-0.96, RMSE=3.8-4.3). Among the 10 urinary metabolites that we measured, 1-hydroxypyrene and 9-hydroxyphenanthrene were associated with methylation aging independently of other OH-PAHs and risk factors; 1-unit increase in 1-hydroxypyrene was associated with a 0.53-y increase in Δage [95% confidence interval (CI): 0.18, 0.88; false discovery rate (FDR) =0.004] and 1.17% increase in aging rate (95% CI: 0.36, 1.98; =0.02), whereas for 9-hydroxyphenanthrene, the increase was 0.54-y for Δage (95% CI: 0.17, 0.91; =0.004), and 1.15% for aging rate (95% CI: 0.31, 1.99; =0.02). The association direction was consistent across the three Chinese panels with the association magnitude correlating with the panels' exposure levels; the association was validated by methylation data of purified leukocytes. Several cytosine-phosphoguanines, including those located on and , were found associated with both aging indicators and monohydroxy-PAH levels.

Conclusions: We developed a methylation age predictor specific for Chinese populations but also accurate for Caucasian populations. Our findings suggest that exposure to PAHs may be associated with an adverse impact on human aging and epigenetic alterations in Chinese populations. https://doi.org/10.1289/EHP2773.
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http://dx.doi.org/10.1289/EHP2773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108582PMC
June 2018

Age prediction of children and adolescents aged 6-17 years: an epigenome-wide analysis of DNA methylation.

Aging (Albany NY) 2018 05;10(5):1015-1026

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

The DNA methylation age, a good reflection of human aging process, has been used to predict chronological age of adults and newborns. However, the prediction model for children and adolescents was absent. In this study, we aimed to generate a prediction model of chronological age for children and adolescents aged 6-17 years by using age-specific DNA methylation patterns from 180 Chinese twin individuals. We identified 6,350 age-related CpGs from the epigenome-wide association analysis (N=179). 116 known age-related sites in children were confirmed. 83 novel CpGs were selected as predictors from all age-related loci by elastic net regression and they could accurately predict the chronological age of the pediatric population, with a correlation of 0.99 and the error of 0.23 years in the training dataset (N=90). The predictive accuracy in the testing dataset (N=89) was high (correlation=0.93, error=0.62 years). Among the 83 predictors, 49 sites were novel probes not existing on the Illumina 450K BeadChip. The top two predictors of age were on the and genes, which are associated with diabetes and cancer, respectively. Our results suggest that the chronological age can be accurately predicted among children and adolescents aged 6-17 years by 83 newly identified CpG sites.
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http://dx.doi.org/10.18632/aging.101445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990383PMC
May 2018

Cho/Cr ratio at MR spectroscopy as a biomarker for cellular proliferation activity and prognosis in glioma: correlation with the expression of minichromosome maintenance protein 2.

Acta Radiol 2019 Jan 17;60(1):106-112. Epub 2018 Apr 17.

1 Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong Province, PR China.

Background: Magnetic resonance (MR) spectroscopy (H-MRS) has been demonstrated to be useful in grading glioma, but the utility in assessing cellular proliferation activity and prognosis correlated with the expression of minichromosome maintenance protein 2 (MCM2) has not been reported.

Purpose: To explore the correlation between proton MR spectroscopy parameters (including choline [Cho]/creatine [Cr], N-acetyl aspartate [NAA]/Cr, and Cho/NAA ratios) and the expression of MCM2 and to further evaluate whether H-MRS can predict cell proliferative activity and provide prognostic information in high-grade gliomas (HGGs).

Material And Methods: Forty-three patients with histopathologically confirmed gliomas were involved in this study. All patients underwent H-MRS examination before surgery. Proliferative activity of gliomas was evaluated by MCM2 labeling index (LI). Pearson correlation analysis and empiric receiver operating characteristic (ROC) curves were performed. The Kaplan-Meier method and Cox regression were used for survival analysis.

Results: Significant correlation was observed between the Cho/Cr ratio and MCM2 LI ( r = 0.522, P < 0.01); however, there was no correlation between MCM2 LI and the Cho/NAA or NAA/Cr ratios ( r = 0.295, P = 0.55 and r = -0.042, P = 0.788, respectively). According to ROC analysis, MCM2 LI of 50% and Cho/Cr ratio of 2.68 represented the optimized cut-off values, respectively, to distinguish longer or shorter survival than 15 months in HGGs patients. Multivariate analysis revealed that both the Cho/Cr ratio and MCM2 expression were independent prognostic markers.

Conclusion: Cho/Cr ratio has a potential in predicting the expression of MCM2 and can evaluate cell proliferative activity noninvasively. Both the Cho/Cr ratio and MCM2 expression are independent prognostic markers in patients with HGGs.
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http://dx.doi.org/10.1177/0284185118770899DOI Listing
January 2019

Association of Educational Level and Marital Status With Obesity: A Study of Chinese Twins.

Twin Res Hum Genet 2018 04 21;21(2):126-135. Epub 2018 Mar 21.

Department of Epidemiology and Biostatistics,School of Public Health,Peking University,Beijing,China.

The prevalence of overweight and obesity is growing rapidly in many countries. Socioeconomic inequalities might be important for this increase. The aim of this study was to determine associations of body mass index (BMI), overweight and obesity with educational level and marital status in Chinese twins. Participants were adult twins recruited through the Chinese National Twin Registry (CNTR), aged 18 to 79 years, and the sample comprised 10,448 same-sex twin pairs. Current height, weight, educational attainment, and marital status were self-reported. Regression analyses and structural equation models were conducted to evaluate BMI, overweight, and obesity associated with educational level and marital status in both sexes. At an individual level, both educational level and marital status were associated with higher BMI and higher risk of being overweight and obesity in men, while in women the effects of educational level on BMI were in the opposite direction. In within-Monozygotic (MZ) twin-pair analyses, the effects of educational level on BMI disappeared in females. Bivariate structural equation models showed that genetic factors and shared environmental confounded the relationship between education and BMI in females, whereas marital status was associated with BMI on account of significant positive unique environmental correlation apart in both sexes. The present data suggested that marital status and BMI were associated, independent of familiar factors, for both sexes of this study population, while common genetic and shared environmental factors contributed to education-associated disparities in BMI in females.
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http://dx.doi.org/10.1017/thg.2018.8DOI Listing
April 2018

CRISPR/cas9 mediated knockout of an intergenic variant rs6927172 identified IL-20RA as a new risk gene for multiple autoimmune diseases.

Genes Immun 2019 02 23;20(2):103-111. Epub 2018 Feb 23.

The Institute of Epigenetic Medicine, The First Hospital of Jilin University, Changchun, China.

Genetic variants near the tumor necrosis factor-α-induced protein 3 gene (TNFAIP3) at the chromosomal region 6q23 demonstrated significant associations with multiple autoimmune diseases. The signals of associations have been explained to the TNFAIP3 gene, the most likely causal gene. In this study, we employed CRISPR/cas9 genome-editing tool to generate cell lines with deletions including a candidate causal variant, rs6927172, at 140 kb upstream of the TNFAIP3 gene. Interestingly, we observed alterations of multiple genes including IL-20RA encoding a subunit of the receptor for interleukin 20. Using Electrophoretic mobility shift assay (EMSA), Western blotting, and chromatin conformation capture we characterized the molecular mechanism that the DNA element carrying the variant rs6927172 influences expression of IL-20RA and TNFAIP3 genes. Additionally, we developed a new use of the transcription activator-like effector (TALE) to study the role of the variant in regulating expressions of its target genes. In summary, we generated deletion knockouts that included the candidate causal variant rs6927172 in HEK293T cells provided new evidence and mechanism for IL-20RA gene as a risk factor for multiple autoimmune diseases.
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http://dx.doi.org/10.1038/s41435-018-0011-6DOI Listing
February 2019

An Autoimmune Disease-Associated Risk Variant in the Gene Plays a Protective Role in Brucellosis That Is Mediated by the NF-κB Signaling Pathway.

J Clin Microbiol 2018 04 26;56(4). Epub 2018 Mar 26.

The Bethune Institute of Epigenetic Medicine, The First Hospital of Jilin University, Jilin, China

Naturally occurring functional variants (rs148314165 and rs200820567, collectively referred to as TT>A) reduce the expression of the tumor necrosis factor alpha-induced protein 3 () gene, a negative regulator of NF-κB signaling, and predispose individuals to autoimmune disease. In this analysis, we conducted a genetic association study of the TT>A variants in 1,209 controls and 150 patients with brucellosis, an infectious disease, and further assessed the role of the variants in brucellosis. Our data demonstrated that the TT>A variants were correlated with cases of brucellosis ( = 0.002; odds ratio [OR] = 0.34) and with individuals who had a positive serum agglutination test (SAT) result (titer of >1/160) ( = 4.2 × 10; OR = 0.23). A functional study demonstrated that brucellosis patients carrying the protective allele (A) showed significantly lower expression levels of the TNFAIP3 gene in their peripheral blood mononuclear cells and showed increased NF-κB signaling. Monocytes from individuals carrying the A allele that were stimulated with had lower mRNA levels of TNFAIP3 and produced more interleukin-10 (IL-10), IL-6, and IL-1β than those from TT allele carriers. These data showed that autoimmune disease-associated risk variants, TT>A, of the TNFAIP3 locus play a protective role in the pathogenesis of brucellosis. Our findings suggest that a disruption of the normal function of the TNFAIP3 gene might serve as a therapeutic target for the treatment of brucellosis.
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http://dx.doi.org/10.1128/JCM.01363-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869838PMC
April 2018

A functional variant in the OAS1 gene is associated with Sjögren's syndrome complicated with HBV infection.

Sci Rep 2017 12 14;7(1):17571. Epub 2017 Dec 14.

The Bethune Institute of Epigenetic Medicine, The First Hospital of Jilin University, Changchun, China.

Hepatitis B virus (HBV) has been suspected to contribute to several autoimmune diseases, including Sjögren's syndrome (SS), although the exact mechanism is unknown. The 2'-5' oligoadenylate synthetase (OAS1) is one of the most important components of the immune system and has significant antiviral functions. We studied a polymorphism rs10774671 of OAS1 gene in Han Chinese descent. The minor allele G was significantly associated with a decreased risk for SS, anti-SSA-positive SS, and anti-SSA-positive SS complicated with HBV infection, which have not been seen in anti-SSA-negative SS and HBcAb-negative SS patients. Gene expression analysis showed that the risk-conferring A allele was correlated with lower expression of p46 and increased expression of p42, p48, and p44. A functional study of enzymatic activities revealed that the p42, p44, and p48 isoforms display a reduced capacity to inhibit HBV replication in HepG2 cells compared to the normal p46 isoform. Our data demonstrated that the functional variant, rs10774671, is associated with HBV infection and anti-SSA antibody-positive SS. The SAS variant switches the primary p46 isoform to three alternatives with decreased capacities to inhibit HBV replication. These data indicated that individuals harboring the risk allele might be susceptible to hepatitis B infection and SS development.
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http://dx.doi.org/10.1038/s41598-017-17931-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730593PMC
December 2017
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