Publications by authors named "Takashi Tamura"

206 Publications

Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2.

Mycoses 2021 Apr 25. Epub 2021 Apr 25.

Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Background: Dermatophytes showing reduced sensitivity to antifungal agents have emerged in several countries. One terbinafine resistant strain of Trichophyton rubrum, TIMM20092, also showed reduced sensitivity to itraconazole (ITC) and voriconazole (VRC). The expression of two genes (TruMDR2 and TruMDR3) encoding multidrug transporters of the ABC family was found to be highly up-regulated in this strain. Deletion of TruMDR3 in TIMM20092 abolished its resistance to VRC but only slightly reduced its resistance to ITC.

Objectives: We examined the potential of T rubrum to develop resistance to ITC by analysing the mechanism of ITC resistance in TIMM20092.

Methods: The deletion of TruMDR2 by gene replacement was performed in TIMM20092 and one TruMDR3-lacking mutant (∆TruMDR3) previously generated from TIMM20092. TruMDR2 single and TruMDR2/TruMDR3 double mutants (∆TruMDR2 and ∆TruMDR2/3) were successfully obtained, respectively.

Results: The suppression of TruMDR2 was shown to abolish resistance to ITC in TIMM20092 and the TruMDR3-lacking mutant, strongly suggesting that TruMDR2 is a major contributor to ITC resistance in TIMM20092.

Conclusions: Our study highlights the possible role of the ABC transporter TruMDR2 in ITC resistance of T. rubrum.
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http://dx.doi.org/10.1111/myc.13286DOI Listing
April 2021

Computed tomography findings for predicting the future occurrence of pancreatic cancer: value of pancreatic volumetry.

Int J Clin Oncol 2021 Apr 7. Epub 2021 Apr 7.

Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, 641-0012, Japan.

Background: The features of pancreatic parenchyma that tend to progress towards pancreatic cancer (PC) are unknown. We performed volumetry of the pancreas in PC patients using computed tomography (CT) scans acquired before detection of PC, and investigated whether CT findings of pancreatic parenchyma could predict the future occurrence of PC.

Methods: Between April 2009 and March 2017, a total of 3769 patients underwent abdominal contrast-enhanced CT, the scans of which were archived as digital images. Among them, 15 PC patients underwent abdominal CT 6-120 months before diagnosis of PC. This retrospective study compared the 15 PC patients (PC group) with 15 propensity score-matched subjects without PC (non-PC group). Pancreatic volumetry and radiological findings were compared between the two groups.

Results: There were significant differences between the PC and non-PC groups in the volume of the main pancreatic duct (MPD) plus any cystic lesion (P = 0.007), volume of the MPD plus any cystic lesion/body surface area (BSA; P = 0.009), MPD diameter (P = 0.011), and MPD diameter/BSA (P = 0.013). Univariate analysis revealed volume of MPD plus any cystic lesion/BSA ≥ 0.53 mL/m (odds ratio [OR] 38.50, P = 0.002), volume of pancreatic parenchyma/BSA < 27.0 mL/m (OR 12.25, P = 0.030), and MPD diameter/BSA ≥ 1.0 mm/m (OR 13.00, P = 0.006) as significant risk factors for PC.

Conclusions: Quantification of the volume of MPD plus any cystic lesion/BSA, volume of pancreatic parenchyma/BSA, and MPD diameter/BSA on pre-diagnosis CT were useful for predicting the future occurrence of PC.
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http://dx.doi.org/10.1007/s10147-021-01915-xDOI Listing
April 2021

Role of CH-EUS as guidance for EUS-biliary drainage malignant obstruction.

Minerva Gastroenterol (Torino) 2021 Apr 1. Epub 2021 Apr 1.

Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan -

Endoscopic ultrasound (EUS)-guided biliary drainage is the usual method of choice for patients with biliary obstructions difficult to treat by endoscopic retrograde cholangiopancreatography. In some patients, however, the bile duct is difficult to detect during EUS-guided biliary drainage. Contrast-enhanced harmonic endoscopic ultrasound has reportedly been useful for interventional EUS procedures. This study describes five patients who underwent EUS-guided biliary drainage with contrast-enhanced harmonic imaging between April 2017 and March 2020 for malignant biliary obstruction due to bile duct cancer. The procedure was performed through an intrahepatic bile duct approach in three patients and through an extrahepatic bile duct approach in the other two. Although fundamental B-mode EUS was unable to detect the target intrahepatic bile duct because the duct was filled with debris, contrast-enhanced harmonic imaging was able to detect the bile duct by clarifying its border with the hepatic parenchyma. Similarly, in patients who underwent extrahepatic bile duct approach, fundamental B-mode EUS could not distinguish between debris and tumor, whereas contrast-enhanced harmonic EUS was able to differentiate between them. The procedure was technically and clinically successful in all five patients. One patient experienced bleeding as an adverse event. Conclusions: EUS-guided biliary drainage with contrast-enhanced harmonic imaging is useful in detecting the fluid space in bile ducts filled with debris or filled with debris and tumor invasion.
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http://dx.doi.org/10.23736/S2724-5985.21.02859-XDOI Listing
April 2021

A new l-arginine oxidase engineered from l-glutamate oxidase.

Protein Sci 2021 May 3;30(5):1044-1055. Epub 2021 Apr 3.

Department of Macromolecular Science, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.

The alternation of substrate specificity expands the application range of enzymes in industrial, medical, and pharmaceutical fields. l-Glutamate oxidase (LGOX) from Streptomyces sp. X-119-6 catalyzes the oxidative deamination of l-glutamate to produce 2-ketoglutarate with ammonia and hydrogen peroxide. LGOX shows strict substrate specificity for l-glutamate. Previous studies on LGOX revealed that Arg305 in its active site recognizes the side chain of l-glutamate, and replacement of Arg305 by other amino acids drastically changes the substrate specificity of LGOX. Here we demonstrate that the R305E mutant variant of LGOX exhibits strict specificity for l-arginine. The oxidative deamination activity of LGOX to l-arginine is higher than that of l-arginine oxidase form from Pseudomonas sp. TPU 7192. X-ray crystal structure analysis revealed that the guanidino group of l-arginine is recognized not only by Glu305 but also Asp433, Trp564, and Glu617, which interact with Arg305 in wild-type LGOX. Multiple interactions by these residues provide strict specificity and high activity of LGOX R305E toward l-arginine. LGOX R305E is a thermostable and pH stable enzyme. The amount of hydrogen peroxide, which is a byproduct of oxidative deamination of l-arginine by LGOX R305E, is proportional to the concentration of l-arginine in a range from 0 to 100 μM. The linear relationship is maintained around 1 μM of l-arginine. Thus, LGOX R305E is suitable for the determination of l-arginine.
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http://dx.doi.org/10.1002/pro.4070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040864PMC
May 2021

Genome-wide association study of serum prostate-specific antigen levels based on 1000 Genomes imputed data in Japanese: the Japan Multi-Institutional Collaborative Cohort Study.

Nagoya J Med Sci 2021 Feb;83(1):183-194

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study, we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance ( <5×10), and eight variants on three chromosomes (chromosomes 12, 14, 15) had genome-wide suggestive levels of significance ( <1×10). With an independent data set from the J-MICC Shizuoka Study (n = 2,447), the association of the SNP with blood PSA levels was not replicated. Although our GWAS failed to detect novel loci associated with serum PSA levels in the Japanese cohort, it confirmed the significant effects of previously reported genetic loci on PSA levels in Japanese. Importantly, our results confirmed the significance of SNPs also in Japanese, implying that consideration of individual genetic information in prostate cancer diagnosis may be possible in the future.
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http://dx.doi.org/10.18999/nagjms.83.1.183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938099PMC
February 2021

Multiple mutations in RNA polymerase β-subunit gene (rpoB) in Streptomyces incarnatus NRRL8089 enhance production of antiviral antibiotic sinefungin: modeling rif cluster region by density functional theory.

Biosci Biotechnol Biochem 2021 Apr;85(5):1275-1282

The Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan.

Streptomyces incarnatus NRRL8089 produces the antiviral, antifungal, antiprotozoal nucleoside antibiotic sinefungin. To enhance sinefungin production, multiple mutations were introduced to the rpoB gene encoding RNA polymerase (RNAP) β-subunit at the target residues, D447, S453, H457, and R460. Sparse regression analysis using elastic-net lasso-ridge penalties on previously reported H457X mutations identified a numeric parameter set, which suggested that H457R/Y/F may cause production enhancement. H457R/R460C mutation successfully enhanced the sinefungin production by 3-fold, while other groups of mutations, such as D447G/R460C or D447G/H457Y, made moderate or even negative effects. To identify why the rif cluster residues have diverse effects on sinefungin production, an RNAP/DNA/mRNA complex model was constructed by homology modeling and molecular dynamics simulation. The 4 residues were located near the mRNA strand. Density functional theory-based calculation suggested that D447, H457, and R460 are in direct contact with ribonucleotide, and partially positive charges are induced by negatively charged chain of mRNA.
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http://dx.doi.org/10.1093/bbb/zbab011DOI Listing
April 2021

Demographics, practice patterns and long-term outcomes of patients with non-ST-segment elevation acute coronary syndrome in the past two decades: the CREDO-Kyoto Cohort-2 and Cohort-3.

BMJ Open 2021 02 22;11(2):e044329. Epub 2021 Feb 22.

Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Objectives: To evaluate patient characteristics and long-term outcomes in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) in the past two decades.

Design: Multicenter retrospective study.

Setting: The Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) Registry Cohort-2 (2005-2007) and Cohort-3 (2011-2013).

Participants: 3254 patients with NSTEACS who underwent first coronary revascularisation.

Primary And Secondary Outcome Measures: The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, cardiac death, sudden cardiac death, non-cardiovascular death, non-cardiac death, myocardial infarction, definite stent thrombosis, stroke, hospitalisation for heart failure, major bleeding, any coronary revascularisation and target vessel revascularisation.

Results: Patients in Cohort-3 were older and more often had heart failure at admission than those in Cohort-2. The prevalence of PCI, emergency procedure and guideline-directed medical therapy was higher in Cohort-3 than in Cohort-2. In patients who received PCI, the prevalence of transradial approach, drug-eluting stent use and intravascular ultrasound use was higher in Cohort-3 than in Cohort-2. There was no change in 3-year adjusted mortality risk from Cohort-2 to Cohort-3 (HR 1.00, 95% CI 0.83 to 1.22, p=0.97). Patients in Cohort-3 compared with those in Cohort-2 were associated with lower adjusted risks for stroke (HR 0.65, 95% CI 0.46 to 0.92, p=0.02) and any coronary revascularisation (HR 0.76, 95%CI 0.66 to 0.87, p<0.001), but with higher risk for major bleeding (HR 1.25, 95% CI 1.06 to 1.47, p=0.008). The unadjusted risk for definite stent thrombosis was lower in Cohort-3 than in Cohort 2 (HR 0.29, 95% CI 0.11 to 0.67, p=0.003).

Conclusions: In the past two decades, we did not find improvement for mortality in patients with NSTEACS. We observed a reduction in the risks for definite stent thrombosis, stroke and any coronary revascularisation, but an increase in the risk for major bleeding.
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http://dx.doi.org/10.1136/bmjopen-2020-044329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903127PMC
February 2021

Assessing the relationship between high-sensitivity C-reactive protein and kidney function employing mendelian randomization in a Japanese community based J-MICC Study.

J Epidemiol 2021 Feb 20. Epub 2021 Feb 20.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine.

Background: Inflammation is thought to be a risk factor for kidney disease. However, discussion is controversial whether inflammatory status is either a cause or an outcome of chronic kidney disease. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using mendelian randomization (MR) approaches.

Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IV and IV, based on SNPs previously identified in European and Asian populations. IV and IV explained 3.4% and 3.9% of the variation in hs-CRP, respectively.

Results: Using the IV, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 95%CI: 0.000, -0.019 to 0.020 and -0.003, -0.019 to 0.014). For IV, we found similar results using the IVW and the WM methods (estimate, 95% CI: -0.005, -0.020 to 0.010 and -0.004, -0.020 to 0.012). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IV: -0.008, -0.058 to 0.042; IV: 0.001, -0.036 to 0.036).

Conclusions: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.
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http://dx.doi.org/10.2188/jea.JE20200540DOI Listing
February 2021

Usefulness of EUS-FNA with contrast-enhanced harmonic imaging for diagnosis of gallbladder tumor.

Endosc Ultrasound 2021 Feb 9. Epub 2021 Feb 9.

Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.

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http://dx.doi.org/10.4103/EUS-D-20-00112DOI Listing
February 2021

Structural basis of enzyme activity regulation by the propeptide of l-lysine α-oxidase precursor from .

J Struct Biol X 2021 13;5:100044. Epub 2021 Jan 13.

Department of Macromolecular Science, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan.

Harmuful proteins are usually synthesized as inactive precursors and are activated by proteolytic processing. l-Amino acid oxidase (LAAO) is a flavoenzyme that catalyzes the oxidative deamination of l-amino acid to produce a 2-oxo acid with ammonia and highly toxic hydrogen peroxide and, therefore, is expressed as a precursor. The LAAO precursor shows significant variation in size and the cleavage pattern for activation. However, the molecular mechanism of how the propeptide suppresses the enzyme activity remains unclear except for deaminating/decarboxylating l-phenylalanine oxidase (PAO), which has a short N-terminal propeptide composed of 14 residues. Here we show the inactivation mechanism of the l-lysine oxidase (LysOX) precursor (prLysOX), which has a long N-terminal propeptide composed of 77 residues, based on the crystal structure at 1.97 Å resolution. The propeptide of prLysOX indirectly changes the active site structure to inhibit the enzyme activity. prLysOX retains weak enzymatic activity with strict specificity for l-lysine and shows raised activity in acidic conditions. The structures of prLysOX crystals that soaked in a solution with various concentrations of l-lysine have revealed that prLysOX can adopt two conformations; one is the inhibitory form, and the other is very similar to mature LysOX. The propeptide region of the latter form is disordered, and l-lysine is bound to the latter form. These results indicate that prLysOX uses a different strategy from PAO to suppress the enzyme activity and suggest that prLysOX can be activated quickly in response to the environmental change without proteolytic processing.
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http://dx.doi.org/10.1016/j.yjsbx.2021.100044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844570PMC
January 2021

Both variants of A1CF and BAZ1B genes are associated with gout susceptibility: a replication study and meta-analysis in a Japanese population.

Hum Cell 2021 Mar 31;34(2):293-299. Epub 2021 Jan 31.

Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.

Gout is a common type of acute arthritis that results from elevated serum uric acid (SUA) levels. Recent genome-wide association studies (GWASs) have revealed several novel single nucleotide polymorphism (SNPs) associated with SUA levels. Of these, rs10821905 of A1CF and rs1178977 of BAZ1B showed the greatest and the second greatest significant effect size for increasing SUA level in the Japanese population, but their association with gout is not clear. We examined their association with gout using 1411 clinically-defined Japanese gout patients and 1285 controls, and meta-analyzed our previous gout GWAS data to investigate any association with gout. Replication studies revealed both SNPs to be significantly associated with gout (P = 0.0366, odds ratio [OR] with 95% confidence interval [CI]: 1.30 [1.02-1.68] for rs10821905 of A1CF, P = 6.49 × 10, OR with 95% CI: 1.29 [1.07-1.55] for rs1178977 of BAZ1B). Meta-analysis also revealed a significant association with gout in both SNPs (P = 3.16 × 10, OR with 95% CI: 1.39 [1.17-1.66] for rs10821905 of A1CF, P = 7.28 × 10, OR with 95% CI 1.32 [1.15-1.51] for rs1178977 of BAZ1B). This study shows the first known association between SNPs of A1CF, BAZ1B and clinically-defined gout cases in Japanese. Our results also suggest a shared physiological/pathophysiological background between several populations, including Japanese, for both SUA increase and gout susceptibility. Our findings will not only assist the elucidation of the pathophysiology of gout and hyperuricemia, but also suggest new molecular targets.
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http://dx.doi.org/10.1007/s13577-021-00485-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900071PMC
March 2021

Body mass index and colorectal cancer risk: A Mendelian randomization study.

Cancer Sci 2021 Apr 25;112(4):1579-1588. Epub 2021 Feb 25.

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m ) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.
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http://dx.doi.org/10.1111/cas.14824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019210PMC
April 2021

Investigation of the Physiological, Biochemical and Antifungal Susceptibility Properties of Candida auris.

Mycopathologia 2021 Jan 21. Epub 2021 Jan 21.

General Medical Education and Research Center, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.

Background: Candida auris is an emerging pathogen associated with outbreaks in clinical settings. Isolates of the pathogen have been geographically clustered into four clades with high intra-clade clonality. Pathogenicity varies among the clades, highlighting the importance of understanding these differences.

Objectives: To examine the physiological and biochemical properties of each clade of C. auris to improve our understanding of the fungus.

Methods: Optimal growth temperatures of four strains from three clades, East Asia, South Asia and South Africa, were explored. Moreover, assimilation and antifungal susceptibility properties of 22 C. auris strains from the three clades were studied.

Results: The optimal growth temperatures of all strains were 35-37 °C. Assimilation testing demonstrated that the commercial API ID 32 C system can be used to reliably identify C. auris based on the biochemical properties of the yeast. Notably, C. auris can be uniquely differentiated from commonly clinical fungi by its ability to assimilate raffinose and inability to utilize D-xylose, suggesting a useful simple screening tool. The antifungal susceptibility results revealed that all strains are resistant against fluconazole (minimal inhibitory concentration (MIC) 4 to > 64 µg/mL) and miconazole (MIC 8 to > 16 µg/mL), with strains from the Japanese lineage showing relatively lower MIC values (1-4 µg/mL). Conversely, itraconazole, voriconazole, amphotericin B, micafungin and caspofungin were active against most of the tested strains. On the clade level, East Asian strains generally showed lower MICs against azoles comparing to the other clades, while they displayed MICs against flucytosine higher than those of strains from South Africa and South Asia clades.

Conclusion: Our data suggest a simple identification approach of C. auris based on its physiological and biochemical properties and highlight aspects of C. auris population from various clades.
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http://dx.doi.org/10.1007/s11046-020-00526-wDOI Listing
January 2021

Association of self-reported moderate vegetable juice intake with small decline in kidney function in a five-year prospective study.

Nutrition 2021 04 10;84:111114. Epub 2020 Dec 10.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives: Although consumption of vegetable and 100% fruit juices are an acceptable alternative for vegetable and fruit intake, information about their actual effects on kidney function is sparse. The aim of this study was to determine the association between the consumption of vegetable and fruit juices and changes in kidney function in a Japanese population over a 5-y period.

Methods: In this prospective study, we analyzed 2755 Japanese (742 men and 2013 women) individuals who participated in both the baseline and follow-up surveys in the Daiko study (a study within the Japan Multi-Institutional Collaborative Cohort study). Estimated glomerular filtration rate (eGFR) was calculated by age, sex, and serum creatinine level. For each beverage, we categorized all participants into four groups-rare (rarely consumed), low (≤2 cups/wk), moderate (3-4 cups/wk), or frequent (≥5 cups/wk) consumers of the beverage-based on a food frequency questionnaire.

Results: The mean baseline and follow-up eGFR (SD) were 82.4 (14.6) and 72.2 (12.6), respectively. In fully adjusted regression analyses, moderate consumption of vegetable juice was associated a lower decline in eGFR compared with the rare consumption group (β = -1.30; P = 0.01). Moreover, stratified analyses revealed that this significant association remained in those who were young, female, non-obese, normotensive, smoked cigarettes, consumed alcohol, or exercised. However, no significant association was found in analyses for fruit juices.

Conclusions: This 5-y prospective study suggested an association between self-reported moderate consumption of vegetable juice and changes (possibly smaller decline) in kidney function in a relatively healthy Japanese population.
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http://dx.doi.org/10.1016/j.nut.2020.111114DOI Listing
April 2021

Comparison of Outcomes of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting Among Patients With Three-Vessel Coronary Artery Disease in the New-Generation Drug-Eluting Stents Era (From CREDO-Kyoto PCI/CABG Registry Cohort-3).

Am J Cardiol 2021 04 14;145:25-36. Epub 2021 Jan 14.

Department of Cardiovascular Surgery, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.

There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG.
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http://dx.doi.org/10.1016/j.amjcard.2020.12.076DOI Listing
April 2021

Structural basis for substrate specificity of l-methionine decarboxylase.

Protein Sci 2021 Mar 21;30(3):663-677. Epub 2021 Jan 21.

Department of Biofunctional Chemistry, Okayama University, Okayama, Japan.

l -Methionine decarboxylase (MetDC) from Streptomyces sp. 590 is a vitamin B -dependent enzyme and catalyzes the non-oxidative decarboxylation of l -methionine to produce 3-methylthiopropylamine and carbon dioxide. We present here the crystal structures of the ligand-free form of MetDC and of several enzymatic reaction intermediates. Group II amino acid decarboxylases have many residues in common around the active site but the residues surrounding the side chain of the substrate differ. Based on information obtained from the crystal structure, and mutational and biochemical experiments, we propose a key role for Gln64 in determining the substrate specificity of MetDC, and for Tyr421 as the acid catalyst that participates in protonation after the decarboxylation reaction.
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http://dx.doi.org/10.1002/pro.4027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888583PMC
March 2021

Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study.

Dig Endosc 2021 Jan 7. Epub 2021 Jan 7.

Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.

Objectives: This single-center comparative randomized superiority study compared biliary stenting using fully covered self-expandable metal stents (FCSEMS) and biliary stenting using plastic stents (PS) in preoperative biliary drainage of patients with borderline resectable pancreatic cancer (BRPC) who are planned to undergo a single regimen of neo-adjuvant chemotherapy (NAC).

Methods: Twenty-two patients with BRPC who required preoperative biliary drainage before NAC (Gemcitabine plus Nab-paclitaxel) were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was the rate of stent dysfunction until surgery or tumor progression. Secondary endpoints were stent patency, number of re-interventions, adverse events of endoscopic retrograde biliary drainage (EBD), operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs.

Results: Eleven patients in each of the groups reached the primary endpoint. The FCSEMS group showed a significantly lower rate of stent dysfunction (18.2% vs. 72.8%, P = 0.015), longer stent patency (P = 0.02), and lower number of re-interventions for stent dysfunction (0.27 ± 0.65 vs. 1.27 ± 1.1, P = 0.001) than the PS group. The adverse events of EBD, operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs did not significantly differ between the two groups.

Conclusions: In patients with BRPC for preoperative biliary drainage, stent dysfunction occurred less frequently with FCSEMSs than with PSs. In addition, FCSEMS and PS provided similar preoperative management of BRPC in terms of the safety of surgery and medical costs. (UMIN ID000030473).
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http://dx.doi.org/10.1111/den.13926DOI Listing
January 2021

Application of the Modified High Bleeding Risk Criteria for Japanese Patients in an All-Comers Registry of Percutaneous Coronary Intervention - From the CREDO-Kyoto Registry Cohort-3.

Circ J 2020 Dec 8. Epub 2020 Dec 8.

Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center.

Background: The prevalence of and expected bleeding event rate in patients with the Japanese version of high bleeding risk (J-HBR) criteria are currently unknown in real-world percutaneous coronary intervention (PCI) practice.Methods and Results:We applied the J-HBR criteria in the multicenter CREDO-Kyoto registry cohort-3 that enrolled 13,258 consecutive patients who underwent first PCI. The J-HBR criteria included Japanese-specific major criteria such as heart failure, low body weight, peripheral artery disease and frailty in addition to the Academic Research Consortium (ARC)-HBR criteria. There were 8,496 patients with J-HBR, and 4,762 patients without J-HBR. The J-HBR criteria identified a greater proportion of patients with HBR than did ARC-HBR (64% and 48%, respectively). Cumulative incidence of the Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was significantly higher in the J-HBR group than in the no-HBR group (14.0% vs. 4.1% at 1 year; 23.1% vs. 8.4% at 5 years, P<0.0001). Cumulative 5-year incidence of BARC 3/5 bleeding was 25.1% in patients with ARC-HBR, and 23.1% in patients with J-HBR. Cumulative incidence of myocardial infarction or ischemic stroke was also significantly higher in the J-HBR group than in the no-HBR group (6.9% vs. 3.6% at 1 year; 13.2% vs. 7.1% at 5 years, P<0.0001).

Conclusions: The J-HBR criteria successfully identified those patients with very high bleeding risk after PCI, who represented 64% of patients in this all-comers registry.
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http://dx.doi.org/10.1253/circj.CJ-20-0836DOI Listing
December 2020

A genome-wide association study in Japanese identified one variant associated with a preference for a Japanese dietary pattern.

Eur J Clin Nutr 2020 Dec 6. Epub 2020 Dec 6.

Department of Preventive Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

Background/objectives: Individual eating habits may be influenced by genetic factors, in addition to environmental factors. Previous studies suggested that adherence to Japanese food patterns was associated with a decreased risk of all-cause and cardiovascular disease mortality. We conducted a genome-wide association study (GWAS) in a Japanese population to find genetic variations that affect adherence to a Japanese food pattern.

Subjects/methods: We analyzed GWAS data using 14,079 participants from the Japan Multi-Institutional Collaborative Cohort study. We made a Japanese food score based on six food groups. Association of the imputed variants with the Japanese food score was performed by linear regression analysis with adjustments for age, sex, total energy intake, alcohol intake (g/day), and principal components 1-10 omitting variants in the major histocompatibility region.

Results: We found one SNP in the 14q11.2 locus that was significantly associated with the Japanese food score with P values <5 × 10. Functional annotation revealed that the expression levels of two genes (BCL2L2, SLC22A17) were significantly inversely associated with this SNP. These genes are known to be related to olfaction and obesity.

Conclusion: We found a new SNP that was associated with the Japanese food score in a Japanese population. This SNP is inversely associated with genes link to olfaction and obesity.
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http://dx.doi.org/10.1038/s41430-020-00823-zDOI Listing
December 2020

Novel endoscopic ultrasonography imaging technique for visualizing microcirculation without contrast enhancement in subepithelial lesions: Prospective study.

Dig Endosc 2020 Nov 3. Epub 2020 Nov 3.

Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.

Objectives: Detective flow imaging for endoscopic ultrasonography (DFI-EUS) is a new imaging modality developed for detecting fine vessels without using ultrasound contrast agents. This study aimed to evaluate its utility by comparing it with a type of directional power Doppler (eFLOW) for subepithelial lesions (SELs).

Methods: Between January 2019 and January 2020, 28 patients with SELs undergoing DFI-EUS and eFLOW-EUS were enrolled. DFI-EUS and eFLOW-EUS assessing the vascularity in SELs were compared in terms of the rates of identification of intratumoral vessels. We also investigated how large vessels were depicted in both modalities based on surgical specimens as well as the detection rates of intratumoral vessels in gastrointestinal stromal tumors (GISTs) and non-GISTs using either DFI-EUS or eFLOW-EUS.

Results: Among 28 patients, 23 with pathological confirmation by EUS-guided fine-needle aspiration biopsy (EUS-FNAB) specimens were included. Of those 23 patients, the 10 who underwent surgical resection were selected for analysis. The rate of detection of intratumoral vessels in SELs was significantly higher on DFI-EUS (80%) than on eFLOW-EUS (30%) (P = 0.03). Comparison with surgical specimens revealed that detection rate for vessels with maximum size of less 1000 μm was higher in DFI-EUS (66%) than that in eFLOW-EUS (0%). GIST patients had significantly higher positive rates (90%) of intratumoral vessels than non-GIST patients (31%) on DFI in 23 cases including EUS-FNAB specimens (P = 0.045).

Conclusions: Detective flow imaging-EUS is more sensitive for depicting intratumoral vessels than eFLOW-EUS. Evaluation of intratumoral vessels on DFI-EUS is useful for identifying GISTs without contrast agents.
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http://dx.doi.org/10.1111/den.13889DOI Listing
November 2020

Association between plasma levels of homocysteine, folate, and vitamin B, and dietary folate intake and hypertension in a cross-sectional study.

Sci Rep 2020 10 28;10(1):18499. Epub 2020 Oct 28.

Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B, and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41-3.96) in men and 1.86 (95% CI 1.11-3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B.
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http://dx.doi.org/10.1038/s41598-020-75267-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595187PMC
October 2020

Endoscopic ultrasound-guided fine needle aspiration with contrast-enhanced harmonic imaging for diagnosis of gallbladder tumor (with video).

J Hepatobiliary Pancreat Sci 2021 Jan 10;28(1):e1-e3. Epub 2020 Nov 10.

Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.

Highlight Endoscopic ultrasound-guided fine needle aspiration with contrast-enhanced harmonic imaging is useful for accurately and safely obtaining tissue from a gallbladder tumor. Tamura and colleagues demonstrate how contrast-enhanced harmonic endoscopic ultrasound facilitates puncturing the gallbladder tumor while avoiding fluid spaces as it demarcates the borderline between the tumor and fluid spaces.
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http://dx.doi.org/10.1002/jhbp.834DOI Listing
January 2021

Association between alcohol intake pattern and metabolic syndrome components and simulated change by alcohol intake reduction: A cross-sectional study from the Japan Multi-Institutional Collaborative Cohort Study.

Alcohol 2020 12 28;89:129-138. Epub 2020 Sep 28.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.

To investigate the association between alcohol intake pattern in amount and frequency and metabolic syndrome (Mets) components, we simulated the change in the prevalence of Mets components by intake reduction. In order to manage Mets, alcohol intake reduction with moderation of intake pattern is required. However, evidence investigating the comparative impact of alcohol intake reduction in amount and frequency for Mets components is limited. We conducted a large-scale cross-sectional study in the general Japanese population. The study subjects included 37,371 non-drinkers and current drinkers recruited in the Japan Multi-Institutional Collaborative Cohort Study. Odds ratios (ORs) for Mets components according to alcohol intake amount and frequency were estimated using a multiple logistic regression model. The prevalence of Mets components was estimated after assumed alcohol intake reduction of a) none, b) 10 g/day (men) or 5 g/day (women), c) 20 g/day (men) or 10 g/day (women), d) less than 20 g/day (men) or 10 g/day (women) for moderate-to-heavy drinkers, e) 1-2 times/week, and f) 3-4 times/week. The ORs with alcohol intake amount and frequency increased with high blood pressure while decreasing with dyslipidemia. A J-shaped association was observed between intake amount and Mets. The estimated prevalence (%) of high blood pressure and dyslipidemia in men were a) 45.2, b) 43.0, c) 41.4, d) 40.4, e) 42.9, and f) 42.0; and a) 50.3, b) 51.8, c) 52.9, d) 50.2, e) 52.7, and f) 53.4 in women. The estimated prevalence of high blood pressure in women did not evidently decrease. Simulated alcohol intake reduction showed decreased prevalence for high blood pressure and increased prevalence for dyslipidemia in men after reduced intake amount and frequency. The largest decreased prevalence for high blood pressure was observed in men when all moderate-to-heavy drinkers reduced their alcohol intake amount to less than 20 g/day.
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http://dx.doi.org/10.1016/j.alcohol.2020.09.002DOI Listing
December 2020

Study profile of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study.

J Epidemiol 2020 Sep 19. Epub 2020 Sep 19.

Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences.

Background: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants.

Methods: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history, and collected peripheral blood samples.

Results: The baseline survey included 92,610 adults (mean age: 55.2 [9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women.

Conclusions: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.
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http://dx.doi.org/10.2188/jea.JE20200147DOI Listing
September 2020

A genome-wide association study on fish consumption in a Japanese population-the Japan Multi-Institutional Collaborative Cohort study.

Eur J Clin Nutr 2021 Mar 7;75(3):480-488. Epub 2020 Sep 7.

Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Background/objective: Although benefits of fish consumption for health are well known, a significant percentage of individuals dislike eating fish. Fish consumption may be influenced by genetic factors in addition to environmental factors. We conducted a genome-wide association study (GWAS) to find genetic variations that affect fish consumption in a Japanese population.

Methods: We performed a two-stage GWAS on fish consumption using 13,739 discovery samples from the Japan Multi-Institutional Collaborative Cohort study, and 2845 replication samples from the other population. We used a semi-quantitative food frequency questionnaire to estimate food intake. Association of the imputed variants with fish consumption was analyzed by separate linear regression models per variant, with adjustments for age, sex, energy intake, principal component analysis components 1-10, and alcohol intake (g/day). We also performed conditional analysis.

Results: We found 27 single nucleotide polymorphisms (SNPs) located in 12q24 and 14q32.12 that were associated with fish consumption. The 19 SNPs were located at 11 genes including six lead SNPs at the BRAP, ACAD10, ALDH2, NAA25, and HECTD4 regions on 12q24.12-13, and CCDC197 region on 14q32.12. In replication samples, all five SNPs located on chromosome 12 were replicated successfully, but the one on chromosome 14 was not. Conditional analyses revealed that the five lead variants in chromosome 12 were in fact the same signal.

Conclusion: We found that new SNPs in the 12q24 locus were related to fish intake in two Japanese populations. The associations between SNPs on chromosome 12 and fish intake were strongly confounded by drinking status.
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http://dx.doi.org/10.1038/s41430-020-00702-7DOI Listing
March 2021

Structural basis of strict substrate recognition of l-lysine α-oxidase from Trichoderma viride.

Protein Sci 2020 11 17;29(11):2213-2225. Epub 2020 Sep 17.

Department of Macromolecular Science, Graduate School of Science, Osaka University, Osaka, Japan.

l-Lysine oxidase (LysOX) is a FAD-dependent homodimeric enzyme that catalyzes the oxidative deamination of l-lysine to produce α-keto-ε-aminocaproate with ammonia and hydrogen peroxide. LysOX shows strict substrate specificity for l-lysine, whereas most l-amino acid oxidases (LAAOs) exhibit broad substrate specificity for l-amino acids. Previous studies of LysOX showed that overall structural similarity to the well-studied snake venom LAAOs. However, the molecular mechanism of strict specificity for l-lysine was still unclear. We here determined the structure of LysOX in complex with l-lysine at 1.7 Å resolution. The structure revealed that the hydrogen bonding network formed by D212, D315, and A440 with two water molecules is responsible for the recognition of the side chain amino group. In addition, a narrow hole formed by five hydrophobic residues in the active site contributes to strict substrate specificity. Mutation studies demonstrated that D212 and D315 are essential for l-lysine recognition, and the D212A/D315A double mutant LysOX showed different substrate specificity from LysOX. Moreover, the structural basis of the substrate specificity change has also been revealed by the structural analysis of the mutant variant and its substrate complexes. These results clearly explain the molecular mechanism of the strict specificity of LysOX and suggest that LysOX is a potential candidate for a template to design LAAOs specific to other l-amino acids.
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http://dx.doi.org/10.1002/pro.3946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586907PMC
November 2020

Endoscopic ultrasound-guided biliary drainage for malignant biliary obstruction with surgically altered anatomy: a multicenter prospective registration study.

Therap Adv Gastroenterol 2020 29;13:1756284820930964. Epub 2020 Jul 29.

Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-8509, Japan.

Background: Endoscopic treatment for malignant biliary obstruction (MBO) in patients bearing surgically altered anatomy (SAA) is not well-established. Although endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as a new treatment option for MBO, limited data are available regarding the efficacy and safety of EUS-BD in patients with SAA. We conducted a multicenter prospective registration study to evaluate the efficacy and safety of EUS-BD in this population.

Methods: This study involved 10 referral centers in Japan. Patients with SAA who were scheduled to receive EUS-BD for unresectable MBO between May 2016 and September 2018 were prospectively registered. The primary endpoint was technical success and the secondary outcomes were clinical success, procedure time, procedure-related adverse events (AEs), stent patency, and overall survival.

Results: In total, 40 patients were prospectively enrolled. The surgical reconstruction methods were gastrectomy with Roux-en-Y reconstruction (47.5%), gastrectomy with Billroth-II reconstruction (15%), pancreaticoduodenectomy (27.5%), and hepaticojejunostomy with Roux-en-Y reconstruction (10%). EUS-BD was performed for primary biliary drainage in 31 patients and for rescue biliary drainage in nine patients. Transmural stenting alone (60%), antegrade stenting alone (5%), and a combination of the two techniques (35%) were selected for patients treated with EUS-BD. Technical and clinical success rates were 100% (95% confidence interval, 91.2-100.0%) and 95% (95% confidence interval, 83.1-99.4%), respectively. Mean procedure time was 36.5 min. Early AEs were noted in six patients (15%): three self-limited bile leak, one bile peritonitis, and two pneumoperitonea. Late AEs occurred in six patients (15%): one jejunal ulcer and five stent occlusions. Stent patency rate after 3 months of survival was 95.7% (22/23). Median overall survival was 96 days.

Conclusion: EUS-BD for MBO in patients with SAA appears to be effective and safe not only as a rescue drainage technique after failed endoscopic retrograde cholangiography but also as a primary drainage technique.

Clinical Trial Registration: UMIN000022101.
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http://dx.doi.org/10.1177/1756284820930964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391429PMC
July 2020

Associations between peroxisome proliferator-activated receptor γ (PPAR-γ) polymorphisms and serum lipids: Two cross-sectional studies of community-dwelling adults.

Gene 2020 Dec 2;762:145019. Epub 2020 Aug 2.

Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

Dyslipidemia is a well-established risk factor for cardiovascular disease. Experimental studies have reported that peroxisome proliferator-activated receptor γ (PPAR-γ) regulates adipocyte differentiation, lipid storage, and glucose metabolism. Therefore, we examined the associations between PPAR-γ polymorphisms (rs1801282, rs3856806, rs12497191, rs1151999, and rs1152003) and serum lipids in two cross-sectional studies. In the Shizuoka area of the Japan Multi-Institutional Collaborative Cohort Study, we examined 4,952 participants (3,356 men and 1,596 women) in a baseline survey and 2,245 participants (1,550 men and 695 women) in a second survey 5 years later. Outcome measures were the prevalence of dyslipidemia (low-density lipoprotein-cholesterol [LDL-C] ≥ 140 mg/dl, high-density lipoprotein-cholesterol < 40 mg/dl, triglycerides ≥ 150 mg/dl, and/or use of cholesterol-lowering drugs) and the prevalence of high LDL-C (LDL-C ≥ 140 mg/dl and/or use of cholesterol-lowering drugs). Multivariate odds ratios (ORs) were estimated by using unconditional logistic regression models. A total of 2,114 and 1,431 individuals (42.7% and 28.9%) had dyslipidemia and high LDL-C in the baseline survey, respectively, as did 933 and 716 (41.6% and 31.9%), respectively, in the second survey. In the baseline study, compared with major allele homozygotes, minor allele homozygotes of rs3856806 and rs12497191 had a 42% (OR, 0.58; 95% confidence interval (CI), 0.39-0.85) and 23% (OR, 0.77; 95% CI, 0.60-0.99) lower risk of dyslipidemia, respectively, after adjustment for potential confounding factors. In addition, minor allele homozygotes of rs3856806 had a 45% (OR, 0.55; 95% CI, 0.35-0.86) lower risk of high LDL-C. Similar risk reductions were found in the second survey. In conclusion, rs3856806 and rs12497191 polymorphisms may be related to a lower risk of dyslipidemia and high LDL-C.
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http://dx.doi.org/10.1016/j.gene.2020.145019DOI Listing
December 2020