Genetic variation at the adiponectin locus and risk of type 2 diabetes in women.

Previous data suggesting that polymorphisms in the adiponectin gene were associated with insulin resistance or type 2 diabetes have been inconsistent. We assessed the relationship between five common haplotype-tagging single nucleotide polymorphisms (SNPs) in the adiponectin gene (-11365C>G, -4034A>C, -3964A>G, +45T>G, and +276G>T), haplotypes defined by these SNPs, and the risk of type 2 diabetes by conducting a nested case-control study of 642 incident cases of type 2 diabetes and 995 matching control subjects in the Nurses' Health Study. Overall, we did not observe significant differences in genotype or allele frequencies for the five SNPs between the case and control subjects. After adjustment for diabetes risk factors, the -4034 C/C genotype was associated with a reduced risk of diabetes (odds ratio [OR] compared with the A/A genotype = 0.70, 95% CI 0.50-0.99, P = 0.04). In subgroup analyses, the +276 genotype was significantly associated with diabetes risk only among subjects with peroxisome proliferator-activated receptor-gamma (PPAR gamma) variant 12Ala allele (OR comparing +276 T alleles with the G/G genotype = 1.69, 1.04-2.75, P = 0.035) or among obese subjects (1.46, 1.03-2.08, P = 0.03). These data suggest a potential interaction between the adiponectin genotype and PPAR gamma genotype or obesity, but these analyses should be considered exploratory and require further investigation in larger studies.

[1]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[2]  K. Clément,et al.  Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. , 2002, Human molecular genetics.

[3]  P. Scherer,et al.  A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. , 2002, Diabetes.

[4]  C. Dina,et al.  Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. , 2002, Diabetes.

[5]  P. Havel.  Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin , 2002, Current opinion in lipidology.

[6]  Lee-Ming Chuang,et al.  Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. , 2002, Diabetes care.

[7]  M. Stumvoll,et al.  Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. , 2002, Diabetes.

[8]  J. Weber,et al.  Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[9]  S. Kihara,et al.  Genomic structure and mutations in adipose-specific gene, adiponectin , 2000, International Journal of Obesity.

[10]  E S Lander,et al.  The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. , 2000, Nature genetics.

[11]  J. Manson,et al.  The Nurses' Health Study: 20-year contribution to the understanding of health among women. , 1997, Journal of women's health.

[12]  B. Spiegelman,et al.  AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity (*) , 1996, The Journal of Biological Chemistry.

[13]  Philipp E. Scherer,et al.  A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes (*) , 1995, The Journal of Biological Chemistry.

[14]  J. Manson,et al.  Body weight and mortality among women. , 1995, The New England journal of medicine.

[15]  J. Manson,et al.  A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. , 1991, Archives of internal medicine.

[16]  Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. National Diabetes Data Group. , 1979, Diabetes.