SREBF-1 gene polymorphisms are associated with obesity and type 2 diabetes in French obese and diabetic cohorts

被引:98
作者
Eberlé, D
Clément, K
Meyre, D
Sahbatou, M
Vaxillaire, M
Le Gall, A
Ferré, P
Basdevant, A
Froguel, P
Foufelle, F
机构
[1] Univ Paris 06, INSERM, Unit 465, Paris, France
[2] Hop Hotel Dieu, Dept Nutr, INSERM, F-75181 Paris 04, France
[3] Inst Pasteur, Unit MR 8090, CNRS, Inst Biol, F-59019 Lille, France
[4] Ctr Etud Polymorphisme Humain, Paris, France
[5] Univ London Imperial Coll Sci Technol & Med, Hammersmith Genome Ctr & Genomic Med, London, England
基金
英国医学研究理事会;
关键词
D O I
10.2337/diabetes.53.8.2153
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:2153 / 2157
页数:5
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