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DENND1A和CYP19A1基因变异在土耳其人群个体肥胖易感性中的作用——一项初步研究

The role of DENND1A and CYP19A1 gene variants in individual susceptibility to obesity in Turkish population-a preliminary study.

作者信息

Kadioglu Ela, Altun Beril, İpek Çağrı, Döğer Esra, Bideci Aysun, Attaran Hadi, Çok İsmet

机构信息

Department of Pharmaceutical Toxicology,Faculty of Pharmacy, Gazi University, Hipodrom, 06330, Ankara, Turkey.

Department of Pediatric Endocrinology, Faculty of Medicine, Gazi University, Teknikokullar, 06500, Ankara, Turkey.

出版信息

Mol Biol Rep. 2018 Dec;45(6):2193-2199. doi: 10.1007/s11033-018-4380-8. Epub 2018 Sep 19.

Abstract

Single nucleotide polymorphisms (SNPs), the most common genetic variations in human genome, can manage the predisposition of certain complex diseases or situations such as obesity. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to being overweight or obese and developing related chronic complications such as hypertension, coronary heart disease, diabetes and cancer. The present study comprised of 193 unrelated healthy volunteers (120 females and 73 males) with Turkish origin. Only female adolescents (n = 110) were divided into 2 categories according to their BMI values as overweight (BMI ≥ 25) and normal (18.5 < BMI < 25) according to WHO classification. Genomic DNA was isolated from venous blood samples and genotyping of DENND1A rs10818854 and CYP19A1 rs2414096 variants was performed on Roche Light Cycler 2.0 Real-Time PCR platform. Serum hormone levels were analyzed by Electrochemiluminescent Immunoassay (ECLIA; Roche diagnostics). The genotype distributions were consistent with the Hardy-Weinberg equilibrium for both SNPs in the studied population (p > 0.05). The genotype distribution of DENND1A rs10818854 was determined for the first time in Turkish population and the variant allele frequency was found as 0.095. According to reduced sex hormone-binding globulin levels and increased free androgen index in the present study, obesity was linked with hyperandrogenism in female subjects. Both polymorphisms were investigated as potential genetic susceptibility markers for obesity and neither DENND1A nor CYP19A1 showed any associations.

摘要

单核苷酸多态性(SNPs)是人类基因组中最常见的基因变异,可调控某些复杂疾病或状况(如肥胖)的易感性。基因多态性也起着重要作用,因为它们会影响人群超重或肥胖的易感性以及发生高血压、冠心病、糖尿病和癌症等相关慢性并发症的风险。本研究纳入了193名祖籍为土耳其的无亲缘关系健康志愿者(120名女性和73名男性)。仅将女性青少年(n = 110)根据其BMI值按照世界卫生组织的分类分为超重(BMI≥25)和正常(18.5<BMI<25)两类。从静脉血样本中提取基因组DNA,并在罗氏Light Cycler 2.0实时PCR平台上对DENND1A rs10818854和CYP19A1 rs2414096变异体进行基因分型。采用电化学发光免疫分析法(ECLIA;罗氏诊断)分析血清激素水平。在所研究人群中,两个SNPs的基因型分布均符合哈迪-温伯格平衡(p>0.05)。首次在土耳其人群中确定了DENND1A rs10818854的基因型分布,发现变异等位基因频率为0.095。根据本研究中降低的性激素结合球蛋白水平和升高的游离雄激素指数,肥胖与女性受试者的高雄激素血症有关。对这两种多态性均作为肥胖潜在的遗传易感性标志物进行了研究,结果显示DENND1A和CYP19A1均未显示出任何关联。

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