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Renal function and klotho gene polymorphisms among Uygur and Kazak populations in Xinjiang, China.

ABSTRACT: The association of genetic polymorphisms of klotho gene with aging has not been thoroughly examined. Previous studies showed that longevity in the Uygurs was considerably greater than in Kazaks in Xinjiang. This study aimed to investigate the difference of renal function and Klotho gene polymorphisms between Kazak and Uygur normal populations in Xinjiang, China.A total of 249 Uygur and 386 Kazak clinically normal subjects were included in this study. Four single-nucleotide polymorphisms (rs1207568, rs564481, rs9527025, and rs9536314) of the klotho gene were genotyped using the ABI SNaPshot method. Estimated glomerular filtration rate (eGFR) was calculated according to the Chinese simplified MDRD equation.There were significant differences between Kazak and Uygur healthy populations in both allele frequencies and genotype distributions in rs9527025 and rs9536314 (P<0.05, respectively). When the subjects were divided into 2 groups according to the genotypes of the klotho gene polymorphism, in the GA+AA genotype distributions of the rs1207568, the differences I serum creatinine and estimated glomerular filtration rate between the Kazak and Uygur groups were statistically significant (P<0.05, respectively). In CC genotype of rs564481, serum creatinine was significantly higher in Kazaks compared with Uygurs (P<0.05). In GG genotype of rs9527025, serum creatinine was significantly higher in the Kazak group compared with the Uygur group (P<0.05), as well as in CG+CC genotype of rs9527025 (P<0.05). Serum creatinine was significantly higher in the Kazak group compared with the Uygur group in TT genotype of rs9536314 (P<0.05), as was GT+GG genotype of rs9536314. Haplotype analysis indicated that the frequencies of ACGT, GTGT, and GCCG haplotypes were significantly different between Kazak and Uygur healthy populations (P=0.04, P=0.018, P=0.000, respectively).Significant differences in klotho gene rs9527025 and rs9536314 polymorphisms were found between the Uygur and Kazak populations.

SUBMITTER: Xu X

PROVIDER: S-EPMC4292765 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Renal function and klotho gene polymorphisms among Uygur and Kazak populations in Xinjiang, China.

Xu Xinjuan X Liang Xiaohui X Hu Guangmei G Zhang Junshi J Lei Hong H

Medical science monitor : international medical journal of experimental and clinical research 20150105

<h4>Background</h4>The association of genetic polymorphisms of klotho gene with aging has not been thoroughly examined. Previous studies showed that longevity in the Uygurs was considerably greater than in Kazaks in Xinjiang. This study aimed to investigate the difference of renal function and Klotho gene polymorphisms between Kazak and Uygur normal populations in Xinjiang, China.<h4>Material/methods</h4>A total of 249 Uygur and 386 Kazak clinically normal subjects were included in this study. F ...[more]

PMID: 25556925

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Project description:BackgroundDyslipidemia is a predisposing factor for coronary heart disease (CHD). High-intensity statin therapy is recommended as secondary prevention. ABCB1 and SLCO1B1 genes influence the efficacy and safety of statins. Xinjiang is a multi-ethnic area; however, little is known about the prevalence of dyslipidemia and gene polymorphisms of ABCB1 and SLCO1B1 in minority groups with CHD.ObjectiveTo measure levels of lipid and apolipoprotein and the prevalence of dyslipidemia and gene polymorphisms of ABCB1, SLCO1B1 in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe populations with CHD in Xinjiang.MethodsThis descriptive retrospective study compares lipid levels in ethnic groups using Kruskal-Wallis test or analysis of variance. The study compared gene polymorphisms and the prevalence of dyslipidemia among different ethnic groups using the chi-square test. The lipid profiles in plasma were measured before lipid-lowering therapy using commercially available kits. Genotyping of SLCO1B1 and ABCB1 variants was performed using sequencing by hybridization.ResultsA total of 2218 patients were successfully screened, including 1044 Han, 828 Uygur, 113 Kazak, 138 Hui, 39 Tatar, 36 Kirgiz, and 20 Sibe patients. The overall mean age was 61.8 ± 10.8 years, and 72.5% of participants were male. Dyslipidemia prevalence in these ethnic groups was 42.1, 49.8, 52.2, 40.6, 48.7, 41.7, and 45.0%, respectively. The prevalence of dyslipidemia, high total cholesterol (TC), high triglycerides (TG), and high low density lipoprotein cholesterol (LDL-C) differed significantly among the groups (P = 0.024; P < 0.001; P < 0.001; P < 0.001, respectively). For the Han group, high LDL-C, high TC, and high TG prevalence differed significantly by gender (P = 0.001, P = 0.022, P = 0.037, respectively). The prevalence of high TC, high TG, and low high density lipoprotein cholesterol (HDL-C) differed significantly by gender in the Uygur group (P = 0.006, P = 0.004, P < 0.001, respectively). The prevalence of high TC in Hui patients significantly differed by gender (P = 0.043). These findings suggest that polymorphisms in ABCB1 and C3435T differ significantly across ethnicities (P < 0.001).ConclusionsThe prevalences of dyslipidemia, high TC, high TG, and high LDL-C in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe CHD patients in Xinjiang differed concerning ethnicity. Ethnic, gender, and lifestyle were the key factors that affected the lipid levels of the population. The prevalence of polymorphisms of ABCB1 and C3435T significantly differed across ethnicities. These findings will aid the selection of precision lipid-lowering medications and prevention and treatment of CHD according to ethnicity in Xinjiang.

Project description:The morbidity of coronary artery disease (CAD) in the Uygur population of Xinjiang was much higher than the national average. Clopidogrel is the most commonly used medication worldwide in dual antiplatelet therapy for CAD, and the response of clopidogrel is affected by CYP2C19, PON1, and ABCB1 genetic polymorphisms. The distribution of CYP2C19*17, ABCB1, and PON1 genetic polymorphisms in Han and Uygur populations with CAD of Xinjiang has not been investigated.This study aimed to investigate the frequencies of CYP2C19, PON1, and ABCB1 genetic polymorphisms, and to identify the metabolizer phenotype of CYP2C19 in Han and Uygur populations with CAD in Northwestern Xinjiang, China. We identified 602 Han and 527 Uygur patients from 2014 through 2019 and studied genotypes for selected allele polymorphisms using sequencing by hybridization.There were significantly different allele frequencies and genotype frequencies between the 2 ethnic groups in terms of CYP2C19*2, *3, *17, ABCB1 and PON1, (P < .05). For CYP2C19*17, the frequency of TT genotype was 2.5% in Uygur patients, but it was undetectable in Han patients. In both the intermediate and poor metabolizer groups, the genotypes polymorphisms CYP2C19*2, *3, *17 were significantly less common in Uygur patients than in Han patients (P < .001). By contrast, the proportion of ultra-metabolizers as defined by CYP2C19*2, *3, *17 polymorphisms significantly higher in Uygur patients (18.6%) than in Han patients (1.7%, P < .001). The CYP2C19*2 frequency was significantly different between Han patients and Han healthy groups (P < .001), while the CYP2C19*3 frequency was significantly different between Uygur patients and Uygur healthy groups (P < .001).Our study supports the notion of interethnic differences in terms of CYP2C19, PON1, and ABCB1 polymorphisms and CYP2C19 genotype-defined clopidogrel metabolic groups. These finding could provide valuable data and insights into personalized CAD treatment for the Uygur and Han populations in Xinjiang.

Dataset Information

Renal function and klotho gene polymorphisms among Uygur and Kazak populations in Xinjiang, China.

Publications

Renal function and klotho gene polymorphisms among Uygur and Kazak populations in Xinjiang, China.

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