Hypoadiponectinaemia and High Risk of Type 2 Diabetes Are Associated With Adiponectin-Encoding (ACDC) Gene Promoter Variants in Morbid Obesity: Evidence for a Role of ACDC in Diabesity

Diabetologia. 2005 May;48(5):892-9. doi: 10.1007/s00125-005-1729-z. Epub 2005 Apr 14.

Abstract

Aims/hypothesis: Morbid obesity (BMI>40 kg/m(2)) affecting 0.5-5% of the adult population worldwide is a major risk factor for type 2 diabetes. We aimed to elucidate the genetic bases of diabetes associated with obesity (diabesity), and to analyse the impact of corpulence on the effects of diabetes susceptibility genes.

Methods: We genotyped known single nucleotide polymorphisms (SNPs) in the adiponectin-encoding adipocyte C1q and collagen-domain-containing (ACDC) gene (-11,391G>A, -11,377C>G, +45T>G and +276G>T), the peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala SNP and ACDC exon 3 variants in 703 French morbidly obese subjects (BMI 47.6+/-7.4 kg/m(2)), 808 non-obese subjects (BMI<30 kg/m(2)) and 493 obese subjects (30< or =BMI<40 kg/m(2)).

Results: Two 5'-ACDC SNPs -11,391G>A, -11,377C>G were associated with adiponectin levels (p=0.0003, p=0.008) and defined a "low-level" haplotype associated with decreased adiponectin levels (p=0.0002) and insulin sensitivity (p=0.01) and with a risk of type 2 diabetes that was twice as high (p=0.002). In contrast, the prevalence of the PPARG Pro12Ala was identical in diabetic and normoglycaemic morbidly obese subjects. The PPARG Pro12 allele only displayed a trend of association with type 2 diabetes in the non-obese group. ACDC exon 3 variants were associated with type 2 diabetes in the non-obese group only (odds ratio 7.85, p<0.0001). In contrast, the 5'-ACDC "low-level" haplotype was associated with type 2 diabetes in obese and morbidly obese subjects (odds ratio 1.73 and 1.92) but not in non-obese individuals.

Conclusions/interpretation: These data clarify the contribution of the 5'-ACDC SNPs to the risk of diabesity. Their interaction with corpulence suggests for the first time a different genetic profile of type 2 diabetes in morbidly obese patients compared with in less obese individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin
  • Diabetes Complications / genetics
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / genetics*
  • European Continental Ancestry Group
  • Family
  • Female
  • France
  • Genetic Variation*
  • Genotype
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / deficiency
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Obesity, Morbid / blood
  • Obesity, Morbid / genetics*
  • PPAR gamma / genetics
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic*

Substances

  • Adiponectin
  • Intercellular Signaling Peptides and Proteins
  • PPAR gamma