SREBF-1 gene polymorphisms are associated with obesity and type 2 diabetes in French obese and diabetic cohorts
SREBF-1 gene polymorphisms are associated with obesity and type 2 diabetes in French obese and diabetic cohorts
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DOI：
10.2337/diabetes.53.8.2153
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发表时间：
2004-08-01
期刊：
影响因子：
7.7
通讯作者：
Foufelle, F
中科院分区：
文献类型：
--
作者：
Eberlé, D;Clément, K;Foufelle, F
固醇调节元件结合蛋白（SREBP）-1转录因子通过促进糖酵解、脂肪生成和脂肪生成在能量稳态中发挥核心作用。固醇调节元件结合蛋白基因（SREBF）-1是肥胖和肥胖相关代谢特征如2型糖尿病和血脂异常的良好候选基因。采用PCR/单链构象多态性（single strand conformation polymorphism，SREBF-1）技术对40例无血缘关系的肥胖患者进行SREBF-1基因筛查，共发现19个单核苷酸多态性（single nucleotide polymorphisms，SNPs）。在法国肥胖和非肥胖人群中进行的一项关联研究中，对6个SNPs进行了基因分型。使用两个独立的非肥胖队列的病例对照研究表明，SNP 17（54 G/C，外显子18 c）与病态肥胖相关（比值比分别为1.5，P = 0.006和P = 0.02）。SNP 3（-150G/A，外显子Ia）、SNP 5（-36delG，外显子Ia）和SNP 17被发现处于高度连锁不平衡。（D' > 0.8）。包括这些SNP（C/G/G/T/C/G，HAF 2）的野生型等位基因的单倍型被鉴定为病态肥胖的危险因素（P = 0.003）。在肥胖组中，SNP 3、SNP 5和SNP 17与男性特异性高脂血症相关（分别为P = 0.07、P = 0.01和P = 0.05）。SNP 17还与2型糖尿病（P = 0.03）和糖尿病队列中肾病患病率增加（P = 0.028）相关。我们的研究结果表明SREBF-1基因在代谢性疾病如肥胖、2型糖尿病和血脂异常的遗传易感性中的作用。
Sterol regulatory element-binding protein (SREBP)-1 transcription factors play a central role in energy homeostasis by promoting glycolysis, lipogenesis, and adipogenesis. The sterol regulatory element-binding protein gene (SREBF)-1 is a good candidate gene for obesity and obesity-related metabolic traits such as type 2 diabetes and dyslipidemia. The SREBF-1 molecular screening of 40 unrelated obese patients by PCR/ single-strand conformation polymorphism revealed 19 single nucleotide polymorphisms (SNPs). Six SNPs were genotyped for an association study in large French obese and nonobese cohorts. Case-control studies using two independent nonobese cohorts indicated that SNP17 (54G/C, exon 18c) is associated with morbid obesity (odds ratio 1.5, P = 0.006 and P = 0.02, respectively). SNP3 (-150G/A, exon la), SNP5 (-36delG, exon la), and SNP17 are found in high linkage disequilibrium. (D' > 0.8). The haplotype including wild-type alleles of these SNPs (C/G/G/T/C/G, HAF2) is identified as a risk factor for morbid obesity (P = 0.003). In the obese group, SNP3, SNP5, and SNP17 are associated with male-specific hypertriglyceridemia (P = 0.07, P = 0.01, and P = 0.05, respectively). SNP17 is also associated with type 2 diabetes (P = 0.03) and increased prevalence of nephropathy (P = 0.028) in a diabetic cohort. Our results indicate a role of the SREBF-1 gene in genetic predisposition of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia.