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

Diabetes. 2004 Aug;53(8):2153-7. doi: 10.2337/diabetes.53.8.2153.

Abstract

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 1a), SNP5 (-36delG, exon 1a), 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, HAP2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Child
  • Cohort Studies
  • DNA-Binding Proteins / genetics*
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • France
  • Gene Frequency
  • Humans
  • Hyperlipidemias / genetics
  • Obesity / genetics*
  • Polymorphism, Genetic / genetics*
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors