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PMID: 15830179 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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 ·Vol. 48 ·No. 5 ·2005-05-00 ·Pages 892-9

Vasseur F, Helbecque N, Lobbens S, Vasseur-Delannoy V, Dina C, Clément K, Boutin P, Kadowaki T, Scherer PE, Froguel P

Abstract

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. 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)). 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. 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.

MeSH Terms
Adiponectin Diabetes Complications/genetics Diabetes Mellitus/blood,genetics Family Female France Genetic Variation Genotype Humans Intercellular Signaling Peptides and Proteins/blood,deficiency,genetics Male Obesity, Morbid/blood,genetics PPAR gamma/genetics Polymorphism, Single Nucleotide Promoter Regions, Genetic Whites
Chemicals
Adiponectin Intercellular Signaling Peptides and Proteins PPAR gamma
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Vasseur F
CNRS 8090-Institute of Biology of Lille, Pasteur Institute Lille, Lille, France.
Helbecque N
Lobbens S
Vasseur-Delannoy V
Dina C
Clément K
Boutin P
Kadowaki T
Scherer P E
Froguel P
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Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/s00125-005-1729-z
Published
2005-05-00
Epub
2005-00-14
Pages
892-9
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
Grants
Medical Research Council · G0000477 · United Kingdom
External Links
PubMed source DOI: 10.1007/s00125-005-1729-z View journal details
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