title: Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study.
abstract: The plasma concentration of the adipocyte-derived peptide adiponectin is decreased in patients with obesity and type 2 diabetes. The adiponectin gene is located on chromosome 3q27, where a diabetes susceptibility locus has been mapped. Adiponectin gene polymorphisms (single nucleotide polymorphisms [SNPs]) have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies. Our aim was to assess the contribution of these SNPs in the development of features of the insulin resistance syndrome in a 3-year prospective study in approximately 4,500 French Caucasian subjects from the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. For subjects who were normoglycemic at baseline, the 3-year risk of becoming hyperglycemic (diabetes or impaired fasting glucose) was affected by two SNPs: G-11391A and T45G. For G-11391A, the risk was increased in GA carriers (odds ratio [OR] adjusted for sex [versus GG] = 1.60 [95% CI 1.16-2.20]; P = 0.004). For T45G, it was increased in GG carriers (OR [versus TT] = 2.71 [1.31-5.60]; P = 0.007). After 3 years, GG subjects had a greater increase in BMI (P = 0.009) and waist-to-hip ratio (P = 0.007). Adiponectin levels at baseline were associated with the development of hyperglycemia (P = 0.005), but the predictive effects on the risk for hyperglycemia were independent of adiponectin genotypes. In conclusion, in the DESIR study, variations at the adiponectin locus affect body weight gain, body fat distribution, and onset of hyperglycemia, as well as adiponectin levels. Adiponectin gene SNPs may have several phenotypic effects that co-occur with the development of the metabolic syndrome.
authors.affiliation: EA 3516, Interactions Gènes-Environnement dans les Pathologies Métaboliques à Risque Cardiovasculaire, Faculté Xavier Bichat, Paris, France. fumeron@bichat.inserm.fr
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fumeron
authors.forename: Roberte
authors.initials: R
authors.lastname: Aubert
authors.forename: Afshan
authors.initials: A
authors.lastname: Siddiq
authors.forename: Dina
authors.initials: D
authors.lastname: Betoulle
authors.forename: Frank
authors.initials: F
authors.lastname: Péan
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.forename: Jean
authors.initials: J
authors.lastname: Tichet
authors.forename: Elsie
authors.initials: E
authors.lastname: Wilpart
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Chesnier
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
mesh_terms: D052242:Adiponectin; D000483:Alleles; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005602:France; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins