Adiponectin polymorphisms, adiposity and insulin metabolism: HERITAGE family study and Oulu diabetic study

Aims/hypothesis. Adiponectin is an adiponcytokine with lowered blood levels in obesity and Type 2 diabetes mellitus. We sought to define the specific effects of different alleles of the gene encoding adiponectin. Methods. We studied the associations of adiponectin gene sequence variations with body fat distribution and insulin indices in 503 White and 276 Black subjects of the HERITAGE Family Study cohort and subjects from a Finnish population. Results. The His111 allele frequency of the Tyr111 His polymorphism in Finnish Type 2 diabetic subjects (n = 254) was higher (5.1%) than in control subjects (n = 270) (2.6%; P = 0.033). In the HERITAGE cohort, the His111 allele was associated with a lower insulin sensitivity index (P = 0.018) and a higher acute insulin response to glucose (P = 0.0098) in Whites. Other variants showed associations with adiposity and plasma lipid values only in Blacks. Among Blacks, the IVS2+G62T variant was associated with body fat (P = 0.002) and total cholesterol values (P = 0.005), and the Gly15Gly variant with cholesterol (P = 0.009) and triglyceride (P = 0.05) levels. The haplotype derived from these two polymorphisms was associated with total body fat, while the IVS2+G62T and Tyr111 His-haplotype was associated with body fat and disposition index. Conclusions. The carriers of the His111 allele may have a higher risk of developing Type 2 diabetes mellitus. Racial differences were found between Blacks and Whites in body composition and lipids according to ACDC genotypes. Sequence variants in the adiponectin gene appear to be associated with diabetes and diabetes-related phenotypes.