Publications by authors named "Vandana Rai"

62 Publications

Relation Between Methylenetetrahydrofolate Reductase Polymorphisms (C677T and A1298C) and Migraine Susceptibility.

Indian J Clin Biochem 2022 Jan 20;37(1):3-17. Epub 2021 Sep 20.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, UP 222 003 India.

Migraine is a neurological disorder which impairs the patient's quality of life. Several association studies investigating the association between MTHFR gene C677T and A1298C polymorphisms and susceptibility to migraine were published. But the results were conflicting, so authors performed a meta-analysis of published case control studies to find out the exact association between MTHFR polymorphism and migraine susceptibility. Four databases were searched for suitable studies up to December, 2018. Odds ratios (OR) with 95% confidence intervals (CI) was calculated adopting additive, homozygote, co-dominant, dominant, and recessive genetic models. Results of MTHFR C677T polymorphism studies meta-analysis showed significant association with migraine risk using allele contrast, homozygote, dominant and recessive genetic models (T vs. C: OR = 1.18, 95% CI = 1.00-1.26,  = 0.05; TT vs. CC: OR = 1.24, 95% CI = 1.0-1.5,  = 0.04; CT vs. CC: OR = 1.08, 95% CI = 0.97-1.07,  = 0.25; TT + CT vs. CC: OR = 1.15, 95% CI = 1.0-1.29,  = 0.04; TT vs. CT + CC: OR = 1.97, 95% CI = 1.28-3.42,  = 0.002). However, results of MTHFR A1298 polymorphism studies meta-analysis did not show any association with migraine. Subgroup analysis based on ethnicity and migraine types i.e. migraine with aura (MA) and without aura (MO) were also performed. Results of present meta-analysis indicate overall association between MTHFR C677T polymorphism with migraine in total 24 studies, in Asian population and in MA cases but did not show any association with Caucasian population and MO cases.
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http://dx.doi.org/10.1007/s12291-021-01000-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799834PMC
January 2022

TNFR2 Depletion Reduces Psoriatic Inflammation in Mice by Downregulating Specific Dendritic Cell Populations in Lymph Nodes and Inhibiting IL-23/IL-17 Pathways.

J Invest Dermatol 2022 Jan 26. Epub 2022 Jan 26.

Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA; Arthritis Center, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, Ohio, USA.

TNF-α, a proinflammatory cytokine, is a crucial mediator of psoriasis pathogenesis. TNF-α functions by activating TNFR1 and TNFR2. Anti-TNF drugs that neutralize TNF-α, thus blocking the activation of TNFR1 and TNFR2, have been proven highly therapeutic in psoriatic diseases. TNF-α also plays an important role in host defense; thus, anti-TNF therapy can cause potentially serious adverse effects, including opportunistic infections and latent tuberculosis reactivation. These adverse effects are attributed to TNFR1 inactivation. Therefore, understanding the relative contributions of TNFR1 and TNFR2 has clinical implications in mitigating psoriasis versus global TNF-α blockade. We found a significant reduction in psoriasis lesions as measured by epidermal hyperplasia, characteristic gross skin lesion, and IL-23 or IL-17A levels in Tnfr2-knockout but not in Tnfr1-knockout mice in the imiquimod psoriasis model. Furthermore, imiquimod-mediated increase in the myeloid dendritic cells, TNF/inducible nitric oxide synthase‒producing dendritic cells, and IL-23 expression in the draining lymph nodes were dependent on TNFR2 but not on TNFR1. Together, our results support that psoriatic inflammation is not dependent on TNFR1 activity but is driven by a TNFR2-dependent IL-23/IL-17 pathway activation. Thus, targeting the TNFR2 pathway may emerge as a potential next-generation therapeutic approach for psoriatic diseases.
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http://dx.doi.org/10.1016/j.jid.2021.12.036DOI Listing
January 2022

The association of ABO blood group with the asymptomatic COVID-19 cases in India.

Transfus Apher Sci 2021 Dec 30;60(6):103224. Epub 2021 Jul 30.

Cytogenetics Laboratory Department of Zoology, Banaras Hindu University, India. Electronic address:

The COVID-19 pandemic resulted in multiple waves of infection worldwide. The large variations in case fatality rate among different geographical regions suggest that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group and COVID-19 susceptibility. It was demonstrated that individuals with blood group O are at the lower risk of coronavirus infection. To establish the association of ABO blood group in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies among 509 individuals, collected from three major districts of Eastern Uttar Pradesh region of India. Interestingly, we found neutralising antibodies in a significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). We further estimated that people with blood group AB are at comparatively higher risk of infection than other blood groups. Thus, among the asymptomatic SARS-CoV-2 recovered people blood group AB has highest, whilst individuals with blood group O has lowest risk of infection.
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http://dx.doi.org/10.1016/j.transci.2021.103224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321691PMC
December 2021

Catechol-O-methyltransferase (COMT) Val158Met Polymorphism and Susceptibility to Alcohol Dependence.

Indian J Clin Biochem 2021 Jul 2;36(3):257-265. Epub 2021 Jan 2.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 India.

Catechol-O-methyl transferase (COMT) enzyme catalyzes the metabolism of dopamine and other catechols in the brain. Several articles investigated catechol-O-methyltransferase (COMT) Val158Met polymorphism as risk factor for alcohol dependence (AD) but the results were inconclusive. The aim of present meta-analysis was to evaluate the association of Val158Met (COMT) polymorphism with AD. Authors performed keyword search of the 4 electronic databases-Pubmed, Google Scholar, Springer Link and Science Direct databases up to December 31, 2019. Total eighteen studies that investigated the association of Val158Met polymorphism with AD were retrieved. The pooled results from the meta-analysis (2278 AD cases and 3717 healthy controls) did not show association with AD using all 5 genetic models (allele contrast model OR = 1.02, 95% CI = 0.90-1.14,  = 0.03; homozygote model OR = 1.06, 95% CI = 0.81-1.38,  = 0.69; dominant model OR = 0.99, 95% CI = 0.85-1.14,  = 0.87; co-dominant model OR = 0.97, 95% CI = 0.86-1.11,  = 0.71; recessive model OR = 1.05;95% CI = 0.85-1.29,  = 0.61). Results of subgroup analysis showed that Val158Met is not risk for AD in Asian and Caucasian population. In conclusion, COMT Val158Met is not a risk factor for alcohol dependence.
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http://dx.doi.org/10.1007/s12291-020-00933-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215027PMC
July 2021

FokI polymorphism of the vitamin D receptor (VDR) gene and susceptibility to tuberculosis: Evidence through a meta-analysis.

Infect Genet Evol 2021 08 24;92:104871. Epub 2021 Apr 24.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, UP, India. Electronic address:

Background: Tuberculosis is one of the top ten causes of deaths worldwide. The deficiency of vitamin D was reported to be associated with the increased susceptibility of tuberculosis. Various previous reports were published to check the association of FokI polymorphism of the vitamin D receptor gene with tuberculosis risk. But their results were inconsistent so, we performed a meta-analysis to know the exact relation of the two.

Methods: Different databases were screened up to November 2020 with the keywords "Vitamin D receptor", "VDR", and "FokI", along with "Tuberculosis" and "TB" to find the suitable articles. All the statistical analyses were performed by the Open Meta-Analyst program and all p-values were two-tailed with a significance level of 0.05.

Results: No statistically significant association was observed in the allele contrast model (OR = 1.11, 95%CI = 0.99-1.24, p = 0.05, I = 73.46%), in the dominant model (OR = 1.11, 95%CI = 0.96-1.28, p = 0.14, I = 71.39%), and in the co-dominant model (OR = 1.05, 95%CI = 0.92-1.21, p = 0.41, I = 65.97%). However, a significant association was found in the homozygote model (OR = 1.32, 95%CI = 1.03-1.69, p = 0.02, I = 67.02%) and in the recessive model (OR = 1.26, 95%CI = 1.03-1.54, p = 0.02, I = 58.01%). Further analysis was performed on the bases of the ethnicity. In Asian population a significant association was found in the homozygote model (OR = 1.57, 95%CI = 1.12-2.21, p = 0.008, I = 70.37%) and in the recessive model (OR = 1.43, 95%CI = 1.08-1.89, p = 0.01, I = 63.13%).

Conclusion: In conclusion, a significant association of FokI with tuberculosis susceptibility was found in the overall analysis and in the Asian population.
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http://dx.doi.org/10.1016/j.meegid.2021.104871DOI Listing
August 2021

Population structure and genome-wide association studies in bread wheat for phosphorus efficiency traits using 35 K Wheat Breeder's Affymetrix array.

Sci Rep 2021 04 7;11(1):7601. Epub 2021 Apr 7.

Life Sciences, University of Bristol, 24 Tyndall Avenue, Bristol, BS8 1TQ, UK.

Soil bioavailability of phosphorus (P) is a major concern for crop productivity worldwide. As phosphatic fertilizers are a non-renewable resource associated with economic and environmental issues so, the sustainable option is to develop P use efficient crop varieties. We phenotyped 82 diverse wheat (Triticum aestivum L.) accessions in soil and hydroponics at low and sufficient P. To identify the genic regions for P efficiency traits, the accessions were genotyped using the 35 K-SNP array and genome-wide association study (GWAS) was performed. The high-quality SNPs across the genomes were evenly distributed with polymorphic information content values varying between 0.090 and 0.375. Structure analysis revealed three subpopulations (C1, C2, C3) and the phenotypic responses of these subpopulations were assessed for P efficiency traits. The C2 subpopulation showed the highest genetic variance and heritability values for numerous agronomically important traits as well as strong correlation under both P levels in soil and hydroponics. GWAS revealed 78 marker-trait associations (MTAs) but only 35 MTAs passed Bonferroni Correction. A total of 297 candidate genes were identified for these MTAs and their annotation suggested their involvement in several biological process. Out of 35, nine (9) MTAs were controlling polygenic trait (two controlling four traits, one controlling three traits and six controlling two traits). These multi-trait MTAs (each controlling two or more than two correlated traits) could be utilized for improving bread wheat to tolerate low P stress through marker-assisted selection (MAS).
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http://dx.doi.org/10.1038/s41598-021-87182-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027818PMC
April 2021

Methylenetetrahydrofolate reductase () gene C677T (rs1801133) polymorphism and risk of alcohol dependence: a meta-analysis.

AIMS Neurosci 2021 27;8(2):212-225. Epub 2021 Jan 27.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur-222 003, UP, India.

Alcohol dependence is a complex neuropsychiatric disorder. Numerous studies investigated association between gene C677T (rs1801133) polymorphism and alcohol dependence (AD), but the results of this association remain conflicting. Accordingly, authors conducted a meta-analysis to further investigate such an association. PubMed, Elsevier Science Direct and Springer Link databases were searched for studies on the association between the C677T polymorphism and AD. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed- or random-effects model. Statistical analysis was performed with the software program MetaAnayst and MIX.A total of 11 articles were identified through a search of electronic databases, up to February 28, 2020. The results of the present meta-analysis did not show any association between MTHFR C677T polymorphisms and AD risk (for T vs. C: OR = 1.04, 95% CI = 0.88-1.24; CT vs. CC: OR = 1.02, 95% CI = 0.62-1.68; for TT+CT vs. CC: OR = 1.10, 95% CI = 0.94-1.29; for TT vs. CC: OR = 1.01, 95% CI = 0.66-1.51; for TT vs. CT+CC: OR = 0.97, 95% CI = 0.66-1.40). Results of subgroup analysis showed no significant association between C677T polymorphism with AD in Asian as well as in Caucasian population. In conclusion, C677T polymorphism is not a risk factor for alcohol dependence.
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http://dx.doi.org/10.3934/Neuroscience.2021011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940109PMC
January 2021

Distribution of Methionine Synthase Reductase (MTRR) Gene A66G Polymorphism in Indian Population.

Indian J Clin Biochem 2021 Jan 30;36(1):23-32. Epub 2019 Nov 30.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 India.

Methionine synthase reductase (MTRR) is an important enzyme of the folate/homocysteine pathway. It is responsible for regulation of methionine enzyme by reductive methylation. A common variant A66G is reported in the FMN-binding domain of the gene, which leads to substitution of isoleucine by methionine (I22M) in MTRR enzyme with reduced activity. Reduced catalytic activity of enzyme leads to high homocysteine concentration in blood and increases risk for numerous diseases. The frequency of A66G polymorphism varies in different ethnic groups. The present study has been designed to evaluate the frequency of A66G gene polymorphism in the Eastern UP population by PCR-RFLP method. Along with this we also performed a meta-analysis to evaluate the global prevalence of this polymorphism. Databases were screened to identified the eligible studies. The prevalence of the G allele and GG genotype was determined by the use of prevalence proportion with 95% CI. Open meta-analyst software was used for the meta-analysis. Total 1000 blood samples were analyzed, the frequencies of A and G alleles were 0.35 and 0.65 respectively. Meta-analysis results revealed that the prevalence of G allele and GG genotype were 49.4% (95% CI 40.6-58.1,  ≤ 0.001) and 24.3% (95% CI 17.8-30.9,  ≤ 0.001) respectively. In sub-group meta-analysis, the lowest frequency of G allele was found in South America (32.7%; 95% CI 14.1-51.3,  ≤ 0.001), and highest in Asia (56.4%; 95% CI 39.5-73.3,  ≤ 0.001). The results of the meta-analysis showed that the Asian population has the highest frequency of G allele and highest frequency of the GG genotype was found in the European population.
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http://dx.doi.org/10.1007/s12291-019-00862-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817751PMC
January 2021

Maternal biomarkers for early prediction of the neural tube defects pregnancies.

Birth Defects Res 2021 04 13;113(7):589-600. Epub 2020 Nov 13.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, Uttar Pradesh, India.

Background: Neural tube defects (NTD) are one of the most common congenital birth defects. The reason for the NTD cause is still not completely known, but it is believed that some genetic and environmental factors might play a role in its etiology. Among the genetic factors the polymorphism in the folate gene pathway is crucial. Numerous studies have suggested the possible role of maternal higher plasma concentration of homocysteine and low concentration of folate and cobalamin in the development of NTD but some negative studies are also published.

Aim: Aim of the present was to find out the exact relation between NTD and maternal biomarkers like folate, cobalamin and homocysteine by conducting a meta-analysis.

Method: Different electronic databases were searched for the eligible studies. Standardized mean difference (SMD) with 95% confidence interval (CI) was used to determine association between maternal markers as risk for NTD pregnancy. The p value <0.05 was considered statistically significant in all tests. All the statistical analyses were done in the Open Meta-Analyst program.

Results: The homocysteine is significantly associated with the increased risk of NTD (SMD = 0.57; 95% CI: 0.35-0.80, p = <0.001; I2 = 93.01%), s-folate showed protective role in NTD (SMD = -0.48; 95% CI: -0.77 to -0.19, p = 0.001; I2 = 95.73%), similarly cobalamin is also having protective role (SMD = -0.28; 95% CI: -0.43 to -0.13, p = <0.001; I2 = 80.40%).

Conclusion: In conclusion this study suggest that different maternal biomarkers may be used for the early prediction of the NTDs.
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http://dx.doi.org/10.1002/bdr2.1842DOI Listing
April 2021

Evaluation of COMT Gene rs4680 Polymorphism as a Risk Factor for Endometrial Cancer.

Indian J Clin Biochem 2020 Jan 4;35(1):63-71. Epub 2018 Dec 4.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 India.

Catechol-O-methyletransferase (COMT) enzyme is involved in the inactivation of catecholamine and catechol estrogens. Catechol estrogens have carcinogenic potential and DNA damaging ability. Several studies investigated COMT Val158Met polymorphism as risk factor for endometrial cancer but the results were inconclusive. Hence the objective of present study was to find out exact association between COMT gene Val158Met polymorphism and endometrial cancer by a meta-analysis. Pubmed, Google Scholar, Springer Link and Science Direct databases were searched for case-control articles which investigated COMT Val158Met polymorphism in endometrial cancer cases. All statistical analysis was performed using MetaAnalyst and Mix programs. The results of meta-analysis suggested that there were no association between COMT Val158Met polymorphism and endometrial cancer risk (allele contrast model-OR = 0.97, 95% CI = 0.86-1.10,  = 0.67; co-dominant model-OR = 0.91, 95% CI = 0.77-1.06,  = 0.23; homozygote model-OR = 1.01, 95% CI = 0.84-1.19,  = 0.29; dominant model-OR = 0.93, 95% CI = 0.77-1.11,  = 0.43; recessive model-OR = 1.02, 95% CI = 0.89-1.20,  = 0.62). Publication bias was absent. Subgroup analysis based on source of controls was also performed. In conclusion, results of present meta-analysis showed no association between COMT Val158Met polymorphism and susceptibility to endometrial cancer.
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http://dx.doi.org/10.1007/s12291-018-0799-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995457PMC
January 2020

Catechol-O-methyltransferase gene Val158Met polymorphism and obsessive compulsive disorder susceptibility: a meta-analysis.

Metab Brain Dis 2020 02 26;35(2):241-251. Epub 2019 Dec 26.

VBS Purvanchal University, Jaunpur, Jaunpur, UP, India.

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that affects approximately 1-3% of the general population. It is characterized by disabling obsessions (intrusive unwanted thoughts) and/or compulsions (ritualized repetitive behaviors). Catechol-O-methyltransferase (COMT) enzyme has an important role in inactivation of dopamine and higher dopamine levels may be implicated in OCD, hence COMT gene is a suitable candidate for OCD. Several case-control studies have evaluated the role of COMT Val 158Met (rs4680;472G- > A) polymorphism as a risk factor for OCD but the results remained inconclusive, hence present meta-analysis was designed to find out correct assessment. All studies that investigated the association of COMT gene Val158Met polymorphism with OCD risk, were considered in the present meta-analysis. Statistical analysis was performed with the software program MetaAnalyst. In the current meta-analysis, 14 case-control studies with 1435 OCD cases and 2753 healthy controls were included. The results indicated significant association between COMT Val158Met polymorphism and OCD risk using allele contrast, homozygote and dominant models (OR = 1.14; 95% CI = 1.02-1.27; p = 0.01; OR = 1.33; 95% CI = 1.09-1.62, p = 0.004; OR = 1.14; 95% CI = 1.0-1.32; p = 0.04). In subgroup analysis based on case gender, meta-analysis of male cases showed significant association using all five genetic models (OR = 1.99; 95%CI = 1.42-2.59; p = <0.001; OR = 1.59; 95% CI = 1.20-2.10; p = 0.001), but did not show any association between COMT Val 158Met polymorphism and OCD risk in females. In conclusion, results of present meta-analysis supports that the COMT Val158Met polymorphism is a risk factor for OCD especially for males.
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http://dx.doi.org/10.1007/s11011-019-00495-0DOI Listing
February 2020

Myosin IIA suppresses glioblastoma development in a mechanically sensitive manner.

Proc Natl Acad Sci U S A 2019 07 24;116(31):15550-15559. Epub 2019 Jun 24.

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Jacksonville, FL 32224;

The ability of glioblastoma to disperse through the brain contributes to its lethality, and blocking this behavior has been an appealing therapeutic approach. Although a number of proinvasive signaling pathways are active in glioblastoma, many are redundant, so targeting one can be overcome by activating another. However, these pathways converge on nonredundant components of the cytoskeleton, and we have shown that inhibiting one of these-the myosin II family of cytoskeletal motors-blocks glioblastoma invasion even with simultaneous activation of multiple upstream promigratory pathways. Myosin IIA and IIB are the most prevalent isoforms of myosin II in glioblastoma, and we now show that codeleting these myosins markedly impairs tumorigenesis and significantly prolongs survival in a rodent model of this disease. However, while targeting just myosin IIA also impairs tumor invasion, it surprisingly increases tumor proliferation in a manner that depends on environmental mechanics. On soft surfaces myosin IIA deletion enhances ERK1/2 activity, while on stiff surfaces it enhances the activity of NFκB, not only in glioblastoma but in triple-negative breast carcinoma and normal keratinocytes as well. We conclude myosin IIA suppresses tumorigenesis in at least two ways that are modulated by the mechanics of the tumor and its stroma. Our results also suggest that inhibiting tumor invasion can enhance tumor proliferation and that effective therapy requires targeting cellular components that drive both proliferation and invasion simultaneously.
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http://dx.doi.org/10.1073/pnas.1902847116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681735PMC
July 2019

Methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to epilepsy.

Neurol Sci 2018 Dec 28;39(12):2033-2041. Epub 2018 Sep 28.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003, India.

Background: Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism was reported as risk factor for multiple diseases due to its role in conversion of homocysteine to methionine. The aim of the present meta-analysis was to find out the validity of association of C677T polymorphism with epilepsy susceptibility.

Methods: Pubmed, Science Direct, Springer Link and Google Scholar, databases were searched for relevant studies up to January, 31, 2018. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed using five genetic models. All statistical analysis was done by MetaAnalyst and Mix programs.

Results: Except recessive model, significant association was found between MTHFR C677T polymorphism and epilepsy risk in other four genetic models (T vs C: OR = 1.29, 95% CI = 1.08-1.52, p = 0.004; TT vs CC: OR = 1.48, 95% CI = 1.19-1.82, p = 0.0003; TT + CT vs CC: OR = 1.20, 95% CI = 1.05-1.38, p = 0.008; TT vs CT + CC: OR = 1.35, 95% CI = 1.11-1.62, p = 0.002). Similarly, in the subgroup analysis based on ethnicity, significant association was found in Asian (T vs C: OR = 1.85; 95% CI = 1.15-2.99; p = 0.03) and Caucasian populations (TT vs CC: OR = 1.38; 95% CI = 1.10-1.1.73; p = 0.005). No evidence of heterogeneity and publication bias was detected in present meta-analysis.

Conclusion: In conclusion, results of present meta-analysis suggested that 677T allele of MTHFR is significantly increases the epilepsy susceptibility.
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http://dx.doi.org/10.1007/s10072-018-3583-zDOI Listing
December 2018

"NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk: A Meta-Analysis."

Nutr Cancer 2018 May-Jun;70(4):557-568. Epub 2018 Apr 13.

a Human Molecular Genetics Laboratory, Department of Biotechnology , VBS Purvanchal University , Jaunpur , Uttar Pradesh , India.

Several studies reported that polymorphism C609T (rs1800566) in (NAD(P)H): quinoneoxidoreductase 1 (NQO1) gene is associated with risk to digestive tract (DT) cancers, like esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Authors conducted a meta-analysis to investigate association between C609T polymorphism and DT cancer risk. Eligible studies were extracted from the databases of PubMed, Google Scholar, Science Direct, and Springer Link. All retrieved articles were evaluated. All statistical analyses were performed using Open Meta-Analyst and MIX1.7 programs. A total of 34 studies including 12,043 DT cancer cases and 15,209 healthy controls were included in the present meta- analysis. Results of meta-analysis revealed a significant association between NQO1 C609T polymorphism and DT cancer risk adopting all 5 genetic models (T vs. C: OR = 1.21, 95% CI = 1.11-1.31, p < 0.001; TT vs. CC: OR = 1.48, 95% CI = 1.22-1.79, p < 0.001; TT + CT vs. CC: OR = 1.23, 95% CI = 1.12-1.35, p < 0.001; TT vs. CT + CC: OR = 1.36, 95% CI = 1.15-1.60, p < 0.001; CT vs. CC: OR = 1.16, 95% CI = 1.07-1.27, p < 0.001). In the stratified analysis based on cancer types, significant associations were observed between NQO1 C609T polymorphism and GC (OR = 1.38, 95% CI = 1.11-1.72, p = 0.003) and CRC (OR = 1.18, 95% CI = 1.06-1.30, p = 0.001), but not with EC (OR = 1.16, 95% CI = 0.99-1.35, p = 0.06). Furthermore, stratified analysis based on ethnicity indicated that there was a significant association between NQO1 C609T polymorphism and DT cancer risk in the Asian (TT vs. CC: OR = 1.55, 95% CI = 1.21-2.00, p ≤ 0.001) as well as in Caucasian populations (TT vs. CC: OR = 1.34, 95% CI = 1.04-1.73, p = 0.02). In conclusion, the results of meta-analysis suggested that the NQO1 C609T polymorphism is a risk factor for DT cancers, including GC and CRC.
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http://dx.doi.org/10.1080/01635581.2018.1460674DOI Listing
February 2019

Strong Association of C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene With Nosyndromic Cleft Lip/Palate (nsCL/P).

Authors:
Vandana Rai

Indian J Clin Biochem 2018 Jan 7;33(1):5-15. Epub 2017 Jul 7.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 India.

Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigentic process of DNA methylation. It has been reported that abnormal DNA methylation contributes to the pathogenesis of congenital anomalies. There were many published case control studies assessing the associations of MTHFR C677T polymorphism with risks of nosyndromic cleft lip with and without palate (nsCL/P), but with inconsistent results. To derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified by search of databases including PubMed, Science Direct, Google Scholar and Springer Link up to December, 2015. Finally, a total of 22 studies with 3724 nsCL/P cases and 5275 controls were included in the present meta-analysis. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were pooled to assess the association. Subgroup analysis based on ethnicity was also performed. All statistical analyses were done by MIX program. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased nsCL/P risk in overall population using four genetic models except homozygote model (for T vs. C: OR = 1.24, 95% CI = 1.1-1.4; for TT + CT vs. CC: OR = 1.29, 95% CI = 1.04-1.59; for CT vs. CC: OR = 1.26, 95% CI = 0.98-1.63; for TT vs. CC: OR = 1.02, 95% CI = 0.74-1.4; for TT vs. CT + CC: OR = 1.36, 95% CI = 1.05-1.74). In conclusion, results of present meta-analysis suggested that MTHFR C677T polymorphism is significantly associated with nonsyndromic orofacial cleft.
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http://dx.doi.org/10.1007/s12291-017-0673-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766472PMC
January 2018

Distribution of C677T Gene Polymorphism in Healthy North Indian Population and an Updated Meta-analysis.

Indian J Clin Biochem 2017 Oct 11;32(4):399-410. Epub 2016 Oct 11.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, UP 222 003 India.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate pathway. Several polymorphisms were reported in gene but C677T polymorphism is most studied and it has been reported to be risk factor for several diseases/disorders. The present study was designed to explore the frequency of C677T polymorphism in North Indian healthy population. In addition to this a meta-analysis of published articles was also performed to estimate the global prevalence of C677T polymorphism. A total of 1000 unrelated healthy subjects were selected for C677T polymorphism analysis. Different databases were searched for eligible articles. Prevalence proportion with 95 % CI was used to determine global prevalence of T allele and TT genotype. Meta-analysis was performed by Open meta-analyst. In 1000 blood samples analyzed, the frequency of T allele and TT genotype was 11 and 1 % respectively. Results of the meta-analysis showed that the global prevalence of T allele and TT genotype were 24.0 % (95 % CI 21.7-26.5) and 7.7 % (95 % CI 6.5-8.9) respectively. In sub-group meta-analysis, the lowest frequency of T allele was found in Africans (10.3 %; 95 % CI 3.8-16.8), and highest in Europeans (34.1 %; 95 % CI 31.9-36.3). The frequency of T allele in the North India is 11 %. The results of the meta-analysis showed that the frequency of the T allele and the TT genotype of C677T is highest in the Caucasian population.
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http://dx.doi.org/10.1007/s12291-016-0619-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634971PMC
October 2017

Methylenetetrahydrofolate reductase A1298C genetic variant& risk of schizophrenia: A meta-analysis.

Indian J Med Res 2017 Apr;145(4):437-447

Department of Psychiatry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Background & Objectives: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, whose role in schizophrenia is debatable. Numerous case-control studies have investigated the association of MTHFR A1298C polymorphism with schizophrenia, but results are controversial. The aim of the present study was to find the association between MTHFR A1298C gene polymorphism and schizophrenia.

Methods: PubMed, Google Scholar, Science Direct and Springer link databases were searched for case-control association studies in which MTHFR A1298C polymorphism was investigated as a risk factor for schizophrenia. In all, 19 studies with 4049 cases and 5488 controls were included in this meta-analysis. Odds ratios (ORs) with 95 per cent confidence intervals (CIs) were used as an association measure.

Results: The results of meta-analysis reported a significant association between A1298C polymorphism and schizophrenia risk in overall comparisons in all genetic models (C vs. A: OR=1.13, 95% CI=1.01-1.27, P=0.02; CC vs. AA: OR=1.20, 95% CI=1.03-1.39, P=0.02; AC vs. AA: OR=1.13, 95% CI=1.03-1.23, P=0.009; AC+CC vs. AA: OR=1.14, 95% CI=1.02-1.24, P=0.002; CC vs. AA+AC: OR=1.17, 95% CI=1.01-1.35, P=0.04).

Interpretation & Conclusions: MTHFR A1298C polymorphism was found to be a risk factor for schizophrenia and might have played a significant role in the pathogenesis of schizophrenia.
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http://dx.doi.org/10.4103/ijmr.IJMR_745_14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663157PMC
April 2017

Methylenetetrahydrofolate Reductase C677T Polymorphism and Risk for Male Infertility in Asian Population.

Indian J Clin Biochem 2017 Jul 8;32(3):253-260. Epub 2017 Feb 8.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 India.

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of folate pathway and required for DNA synthesis and methylation. MTHFE C677T polymorphisms is reported as risk factors for various diseases and disorders like birth defects, metabolic, neurological, psychiatric disorders, and cancers. Several studies have investigated association between the MTHFR C677T polymorphism and male infertility. To assess the risk associated with MTHFR C677T polymorphism in Asian population, a meta-analysis was performed. Included articles were collected from the following electronic databases: PubMed, Google Scholar, and Science direct up to March 2015. Risk was estimated as pooled odds ratios (ORs) with confidence intervals (CIs) for assessment. Seventeen case-control studies involving 4392 breast infertile males and 3667 fertile males were found suitable for the inclusion in the present meta-analysis. Results showed that the C677T polymorphism was significantly associated with male infertility in Asian population using all the five genetic models (OR (allele contrast model) = 1.86, 95% CI 1.7-2.0; OR (homozygote model) = 1.96, 95% CI 1.67-2.30; OR (co-dominant model) = 1.40, 95% CI 1.18-1.62; OR (dominant model) = 1.53, 95% CI 1.30-1.77; OR (recessive model) = 1.67, 95% CI 1.44-1.92). In conclusion, results of present meta-analysis strongly supported an association between C677T polymorphism and male infertility in Asians.
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http://dx.doi.org/10.1007/s12291-017-0640-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539015PMC
July 2017

Impact of Catechol-O-Methyltransferase Val 158Met (rs4680) Polymorphism on Breast Cancer Susceptibility in Asian Population

Asian Pac J Cancer Prev 2017 05 1;18(5):1243-1250. Epub 2017 May 1.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur-222 003, UP, India. Email:

Background: Catechol-O-methyltransferase (COMT) is an important estrogen-metabolizing enzyme. Numerous case-control studies have evaluated the role COMT Val 158Met (rs4680;472G->A) polymorphism in the risk of breast cancer and provided inconclusive results, hence present meta-analysis was designed to get a more reliable assessment in Asian population. Methods: A total of 26 articles were identified through a search of four electronic databases- PubMed, Google Scholar, Science Direct and Springer link, up to March, 2016. Pooled odds ratios (ORs) with 95% con¬fidence intervals (CIs) were used as association measure to find out relationship between COMT Val158Metpolymorphism and the risk of breast cancer. We also assessed between study heterogeneity and publication bias. All statistical analyses were done by Open Meta-Analyst. Results: Twenty six case-control studies involving 5,971 breast cancer patients and 7,253 controls were included in the present meta-analysis. The results showed that the COMT Val158Met polymorphism was significantly associated with breast cancer risk except heterozygote model(allele contrast odds ratio (ORAvsG)= 1.13, 95%CI=1.02-1.24,p=0.01; heterozygote/co-dominant ORGAvsGG= 1.03, 95%CI=0.96-1.11,p=0.34; homozygote ORAAvsGG= 1.38, 95%CI= 1.08-1.76,p=0.009; dominant model ORAA+GAvsGG= 1.08, 95%CI=1.01-1.16,p=0.02; and recessive model ORAAvsGA+GG= 1.35, 95%CI=1.07-1.71,p=0.01). In addition, we also performed subgroup analysis based on source of controls and menopausal state of patients. Conclusions: In conclusion, the COMT Val158Met polymorphism was related to increased breast cancer susceptibility in the Asian population.
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http://dx.doi.org/10.22034/APJCP.2017.18.5.1243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555530PMC
May 2017

Myosin IIA Heavy Chain Phosphorylation Mediates Adhesion Maturation and Protrusion in Three Dimensions.

J Biol Chem 2017 02 4;292(8):3099-3111. Epub 2017 Jan 4.

Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195. Electronic address:

Non-muscle myosin II (NMII) is a conserved force-producing cytoskeletal enzyme with important but poorly understood roles in cell migration. To investigate myosin heavy chain (MHC) phosphorylation roles in 3D migration, we expressed GFP-tagged NMIIA wild-type or mutant constructs in cells depleted of endogenous NMIIA protein. We find that individual mutation or double mutation of Ser-1916 or Ser-1943 to alanine potently blocks recruitment of GFP-NM-IIA filaments to leading edge protrusions in 2D, and this in turn blocks maturation of anterior focal adhesions. When placed in 3D collagen gels, cells expressing wild-type GFP MHC-IIA behave like parental cells, displaying robust and active formation and retraction of protrusions. However, cells depleted of NMIIA or cells expressing the mutant GFP MHC-IIA display severe defects in invasion and in stabilizing protrusions in 3D. These studies reveal an NMIIA-specific role in 3D invasion that requires competence for NMIIA phosphorylation at Ser-1916 and Ser-1943. In sum, these results demonstrate a critical and previously unrecognized role for NMIIA phosphorylation in 3D invasion.
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http://dx.doi.org/10.1074/jbc.M116.733402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5336147PMC
February 2017

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis.

Authors:
Vandana Rai

Indian J Clin Biochem 2016 Oct 6;31(4):402-13. Epub 2016 Feb 6.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, UP 222003 India.

The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was implicated to be associated with thrombophilia due to its role in catalyzing the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine. Several case-control studies were investigated MTHFR C677T polymorphism as risk for recurrent pregnancy loss (RPL). These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of RPL whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies published from Asian population relating the C677T polymorphism to the risk of RPL was conducted. The following electronic databases were searched without language restrictions: PubMed, Google Scholars, Elsevier and Springer Link up to December, 2015. Meta-analysis was performed using MetaAnalyst and Mix version 1.7. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased RPL risk in Asian population using all five genetic models (for T vs. C: OR 1.35, 95 % CI 1.09-1.68, p = 0.009; for TT + CT vs. CC: OR 1.44, 95 % CI 1.14-1.82, p = 0.006; for CT vs. CC: OR 1.39, 95 % CI 1.07-1.8, p = 0.01; for TT vs. CC: OR 1.79, 95 % CI 1.23.2.6, p = 0.007; for TT vs. CT + CC: OR 1.61, 95 % CI 1.02-2.56, p = 0.04). In conclusion, this meta-analysis demonstrates a strong association between the MTHFR C677T variant and RPL in Asian population and raising the importance of the use of folate in its treatment and prevention.
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http://dx.doi.org/10.1007/s12291-016-0554-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992492PMC
October 2016

Folate Pathway Gene Methylenetetrahydrofolate Reductase C677T Polymorphism and Alzheimer Disease Risk in Asian Population.

Authors:
Vandana Rai

Indian J Clin Biochem 2016 Jul 23;31(3):245-52. Epub 2015 Jun 23.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 UP India.

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to Alzheimers disease (AD) was controversial in previous studies. The present meta-analysis was designed to investigate the association of MTHFR C677T polymorphism with AD. Nine studies were identified by search of PubMed, Google Scholar, Elsevier, Springer Link databases, up to January 2013. Odds ratios (ORs) with corresponding 95 % confidence interval (CI) were calculated using fixed effects model or random effects model. All statistical analysis was done by Mix version 1.7. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C: OR 1.29, 95 % CI 1.15-1.44, p < 0.0001; for TT + CT vs CC: OR 1.38, 95 % CI 1.16-1.364, p = 0.0002; for TT vs CC: OR 1.60, 95 % CI 1.25-2.04, p = 0.0001; for CT vs CC: OR 1.28, 95 % CI 1.1-1.53, p < 0.008; for TT vs CT + CC: OR 1.37, 95 % CI 1.12-1.67, p = 0.002). Results from present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD in Asian population.
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http://dx.doi.org/10.1007/s12291-015-0512-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910841PMC
July 2016

Increased cancer stem cell invasion is mediated by myosin IIB and nuclear translocation.

Oncotarget 2016 Jul;7(30):47586-47592

Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

Despite many advances in the treatment of breast cancer, it remains one of the leading causes of death among women. One hurdle for effective therapy is the treatment of the highly invasive and tumorigenic subpopulation of tumors called cancer stem cells (CSCs). CSCs, when stimulated with EGF, migrate through a physiological 3D collagen matrix at a higher velocity than non-stem cancer cells (non-SCCs). This increased invasion is due, in part, by an enhanced nuclear translocation ability of CSCs. We observed no difference between CSC and non-SCC in cellular migration rates on a 2D surface. Furthermore, during transwell migration using large diameter transwell pores, both CSC and non-SCC populations migrated with similar efficiency. However, when challenged with more restrictive transwells, CSCs were dramatically more capable of transwell migration. These results implicate nuclear translocation as a major rate limiting factor for CSC dissemination. We further show that non-muscle myosin IIB is critical for this enhanced nuclear translocation and the ability for cancer stem cells to efficiently migrate through restrictive 3D environments. These studies suggest that cytoskeletal elements upregulated in CSCs, such as myosin IIB, may be valuable targets for intervention in cancer stem cell dispersal from tumors.
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http://dx.doi.org/10.18632/oncotarget.9896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216963PMC
July 2016

Role of MTHFR C677T gene polymorphism in the susceptibility of schizophrenia: An updated meta-analysis.

Asian J Psychiatr 2016 Apr 15;20:41-51. Epub 2016 Feb 15.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur 222 003, UP, India. Electronic address:

Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme of folate/homocysteine metabolic pathway. C677T polymorphism of MTHFR gene was reported as risk factor for congenital defects, metabolic and neuropsychiatric disorders. Numerous case-control studies investigated C677T polymorphism as risk factor for schizophrenia but results of these studies were contradictory. To draw a conclusion, a meta-analysis of all available case-control studies was performed. PubMed, Google Scholar, Springer Link and Elsevier databases were searched for eligible case-control studies. Pooled odds ratio with 95%CI was used as an association measure and all statistical analyses were performed by Open Meta-Analyst and MIX software. Total 38 studies with 10,069 cases and 13,372 controls were included in the present meta-analysis. Results of meta-analysis showed significant associated between C677T polymorphism and risk of schizophrenia (ORTvsC=1.18, 95%CI=1.10-1.27, p=<0.001; ORCTvsCC=1.10, 95%CI=1.04-1.17, p=<0.001; ORTTvsCC=1.40, 95%CI=1.20-1.64, p=<0.001; ORTT+CTvsCC=1.19, 95%CI=1.09-1.30, p=<0.001). We also performed subgroup and sensitivity analyses. Subgroup analysis was done according to ethnicity and significant association was found between C677T polymorphism and risk of schizophrenia in all three ethnic populations-African (OR=2.51; 95%CI=1.86-3.40; p=<0.001), Asian (OR=1.21; 95%CI=1.10-1.33; p=<0.001) and Caucasian (OR=1.07; 95%CI=1.01-1.14; p=0.01). In conclusion the results of the present meta-analysis suggested that the MTHFR C677T polymorphism is a risk factor for schizophrenia.
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http://dx.doi.org/10.1016/j.ajp.2016.02.002DOI Listing
April 2016

Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.

Authors:
Vandana Rai

Metab Brain Dis 2016 08 8;31(4):727-35. Epub 2016 Mar 8.

VBS Purvanchal University, Jaunpur, 222003, UP, India.

Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - 'MTHFR', 'C677T', in combination with 'Autism'. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (ORTvs.C = 1.48; 95 % CI: 1.18-1.86; P = 0.0007; ORTT + CT vs. CC = 1.70, 95 % CI = 0.96-2.9, p = 0.05; ORTT vs. CC = 1.84, 95 % CI = 1.12-3.02, p = 0.02; ORCT vs.CC = 1.60, 95 % CI = 1.2-2.1, p = 0.003; ORTT vs.CT+CC = 1.5, 95 % CI = 1.02-2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (ORTvs.C = 1.43; 95 % CI = 1.1-1.87; p = 0.009) and Asian population (ORTvs.C = 1.68; 95 % CI = 1.02-2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism.
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http://dx.doi.org/10.1007/s11011-016-9815-0DOI Listing
August 2016

Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Alzheimer Disease Risk: a Meta-Analysis.

Authors:
Vandana Rai

Mol Neurobiol 2017 03 28;54(2):1173-1186. Epub 2016 Jan 28.

Department of Biotechnology, Human Molecular Genetics Laboratory, VBS Purvanchal University, Jaunpur, 222003, UP, India.

Methylenetetrahydrofolate reductase (MTHFR) is key enzyme of folate/homocysteine pathway. Case control association studies on MTHFR C677T polymorphism and Alzheimer's disease (AD) have been repeatedly performed over the last two decades, but the results are inconclusive. The aim of the present study was to assess the risk of MTHFR C677T polymorphism for AD. Forty-one studies were identified by a search of PubMed, Google Scholar, Elsevier, and Springer Link databases, up to January 2015. Odds ratios (ORs) with corresponding 95 % confidence interval (CI) were calculated using fixed effect model or random effect model. The subgroup analyses based on ethnicity were performed. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C OR = 1.29, 95 % CI = 1.07-1.56, p = 0.003; for TT + CT vs CC OR = 1.29, 95 % CI = 1.19-1.40, p = 0.0004; for TT vs CC OR = 1.31, 95 % CI = 1.16-1.48, p = 0.001; for CT vs CC OR = 1.24, 95 % CI = 1.13-1.35, p < 0.004; and for TT vs CT + CC OR = 1.13, 95 % CI = 1.00-1.28, p = 0.02). Results of present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD.
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http://dx.doi.org/10.1007/s12035-016-9722-8DOI Listing
March 2017

Evaluation of the MTHFR C677T Polymorphism as a Risk Factor for Colorectal Cancer in Asian Populations.

Authors:
Vandana Rai

Asian Pac J Cancer Prev 2015 ;16(18):8093-100

Department of Biotechnology, Faculty of Sciences, VBS Purvanchal University , Jaunpur, India E-mail :

Background: Genetic and environmental factors play important roles in pathogenesis of digestive tract cancers like those in the esophagus, stomach and colorectum. Folate deficiency and methylenetetrahydrofolate reductase (MTHFR) as an important enzyme of folate and methionine metabolism are considered crucial for DNA synthesis and methylation. MTHFR variants may cause genomic hypomethylation, which may lead to the development of cancer, and MTHFR gene polymorphisms (especially C677T and A1298C) are known to influence predispositions for cancer development. Several case control association studies of MTHFR C677T polymorphisms and colorectal cancer (CRC) have been reported in different populations with contrasting results, possibly reflecting inadequate statistical power.

Aim: The present meta-analysis was conducted to investigate the association between the C677T polymorphism and the risk of colorectal cancer.

Materials And Methods: A literature search of the PubMed, Google Scholar, Springer link and Elsevier databases was carried out for potential relevant articles. Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFR C677T with the susceptibility to CRC. Cochran's Q statistic and the inconsistency index (I2) were used to check study heterogeneity. Egger's test and funnel plots were applied to assess publication bias. All statistical analyses were conducted by with MetaAnalyst and MIX version 1.7.

Results: Thirty four case-control studies involving a total of 9,143 cases and 11,357 controls were retrieved according to the inclusion criteria. Overall, no significant association was found between the MTHFR C677T polymorphism and colorectal cancer in Asian populations (for T vs. C: OR=1.03; 95% CI= 0.92-1.5; p= 0.64; for TT vs CC: OR=0.88; 95%CI= 0.74-1.04; p= 0.04; for CT vs. CC: OR = 1.02; 95%CI= 0.93-1.12; p=0.59; for TT+ CT vs. CC: OR=1.07; 95%CI= 0.94-1.22; p=0.87).

Conclusions: Evidence from the current meta-analysis indicated that the C677T polymorphism is not associated with CRC risk in Asian populations. Further investigations are needed to offer better insight into any role of this polymorphism in colorectal carcinogenesis.
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http://dx.doi.org/10.7314/apjcp.2015.16.18.8093DOI Listing
October 2016

Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility.

Meta Gene 2015 Dec 1;6:72-84. Epub 2015 Oct 1.

Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur 222 003, UP, India.

There are several evidences supporting the role of 5-10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in breast cancer (BC). Case control association studies on breast cancer have been repeatedly performed over the last two decades, but results are inconsistent. We performed a meta-analysis to confirm the association between MTHFR C677T polymorphism and BC risk. The articles were retrieved by searching the PubMed, Google Scholar, and Springer Link databases. Crude odds ratios (OR) with 95% confidence intervals (CIs) was used to assess the strength of association between C677T polymorphism and BC. Publication bias was assessed by Egger's and Begg-Mazumdar tests. Meta-analysis was performed with Open Meta Analyst. Total 75 studies with 31,315 cases and 35, 608 controls were found suitable for the inclusion in the present meta-analysis. The results of meta-analysis suggested that there were moderate significant association between C677T polymorphism and BC risk using overall comparisons in five genetic models (T vs. C: OR = 1.08, 95% CI = 1.03-1.13, p = < 0.001; TT + CT vs. CC: OR = 1.06, 95% CI = 1.02-1.09, p = < 0.001; TT vs. CC: OR = 1.17, 95% CI = 1.06-1.28, p = 0.001; CT vs. CC OR = 1.05, 95% CI = 1.01-1.08, p = 0.005; TT vs. CT + CC: OR = 1.12, 95% CI = 1.03-1.22, p = 0.005). In conclusion, results of present meta-analysis showed modest association between MTHFR C677T polymorphism with breast cancer in total studies. However, sub-group analysis results based on ethnicity showed strong significant association between TT genotype and breast cancer (TT vs. CC; OR°=°1.26; 95% CI: 1.06-1.51; p = 0.009) in Asian population but in Caucasian population such association was not observed (TT vs. CC; OR°=°1.08; 95% CI: 0.99-1.14; p = 0.05).
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http://dx.doi.org/10.1016/j.mgene.2015.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634353PMC
December 2015

Folate pathway gene MTHFR C677T polymorphism and risk of lung cancer in Asian populations.

Authors:
Vandana Rai

Asian Pac J Cancer Prev 2014 ;15(21):9259-64

Department of Biotechnology, Human Molecular Laboratory, VBS Purvanchal University, Jaunpur, India E-mail :

Background: Previous studies concerning the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism with lung cancer in Asian populations have provided inconclusive findings.

Aim: A meta-analysis was performed to investigate a more reliable association between MTHFR C677T polymorphism and lung cancer in Asians.

Materials And Methods: A comprehensive search was conducted to identify all case-control studies of MTHFR polymorphisms and lung cancer in Asia, using odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of any association.

Results: Meta-analysis results suggested that the MTHFR C677T polymorphism contributed to an increased lung cancer risk in Asian populations (for T vs C: OR=1.11, 95%CI=1.0-1.23; for CT vs CC: OR= 1.1, 95%CI= 0.95-1.2 ; for TT+CT vs CC: OR=1.13, 95%CI=1.0-1.30; for TT vs CC: OR=1.25, 95%CI=1.01-1.30; for TT vs CT+CC: OR=1.16, 95%CI=1.0-1.36).

Conclusions: MTHFR C677T polymorphism is significantly associated with lung cancer in Asians.
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http://dx.doi.org/10.7314/apjcp.2014.15.21.9259DOI Listing
July 2015

Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India.

Indian J Hum Genet 2014 Apr;20(2):142-7

Department of Biotechnology, Human Molecular Genetics Laboratory, VBS Purvanchal University, Jaunpur, Uttar Pradesh, India.

Background: Down syndrome (DS) is the most common cause of mental retardation of genetic etiology with the prevalence rate of 1/700 to 1/1000 live births worldwide. Several polymorphisms in folate/homocysteine metabolism pathways genes have been reported as a risk factor in women for bearing DS child, but very few studies investigated these polymorphisms in DS cases whether there are a risk factor for being DS or not.

Objective: We have investigated the association of methylenetetrahydrofolate reductase (MTHFR) with the occurrence of DS in Indian population. MTHFR is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine responsible for the reduction of methyltetrahydrofolate. A total of 32 DS cases and 64 age, sex matched controls were genotyped for MTHFR C677T polymorphism by polymerase chain reaction-restriction fragment length polymorphism.

Results: The observed genotype frequencies were CC = 0.81; CT = 0.17 and TT = 0.02 in controls and CC = 0.81 and CT = 0.19 in DS cases. Frequency of T allele in DS and controls were 0.09 and 0.1, respectively. Significant difference in the distribution of mutant 677T allele was not observed between DS cases and controls (odds ratio = 0.915; 95% confidence intervals: 0.331-2.53; P = 0.864).

Conclusion: Results of this study indicate that MTHFR C677T polymorphism is not risk factor for DS.
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http://dx.doi.org/10.4103/0971-6866.142858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228564PMC
April 2014
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