Association of Adiponectin Gene Polymorphisms With Type 2 Diabetes in an African American Population Enriched for Nephropathy

OBJECTIVE—Polymorphisms in the adiponectin gene (ADIPOQ) have been associated with type 2 diabetes and diabetic nephropathy in type 1 diabetes, in mostly European-derived populations.RESEARCH DESIGN AND METHODS—A comprehensive association analysis of 24 single-nucleotide polymorphisms (SNPs) in the adiponectin gene was performed for type 2 diabetes and diabetic nephropathy in African Americans.RESULTS—The minor allele (A) in a single SNP in intron 1 (rs182052) was associated with diabetic nephropathy (P = 0.0015, odds ratio [OR] 1.37, CI 1.13–1.67, dominant model) in an African American sample of 851 case subjects with diabetic nephropathy and 871 nondiabetic control subjects in analyses incorporating adjustment for varying levels of racial admixture. This association remained significant after adjustment of the data for BMI, age, and sex (P = 0.0013–0.0004). We further tested this SNP for association with longstanding type 2 diabetes without nephropathy (n = 317), and evidence of association was also significant (P = 0.0054, OR 1.46, CI 1.12–1.91, dominant model) when compared with the same set of 871 nondiabetic control subjects. Combining the type 2 diabetes and diabetic nephropathy samples into a single group of case subjects (n = 1,168) resulted in the most significant evidence of association (P = 0.0003, OR 1.40, CI 1.17–1.67, dominant model). Association tests between age at onset of type 2 diabetes and the rs182052 genotypes also revealed significant association between the presence of the minor allele (A/A or A/G) and earlier onset of type 2 diabetes.CONCLUSIONS—The SNP rs182052 in intron 1 of the adiponectin gene is associated with type 2 diabetes in African Americans.Type 2 diabetes and diabetic nephropathy are more prevalent among African Americans than European Americans, even when taking into consideration ethnic differences in socioeconomic status, prevalence and severity of hypertension, and access to adequate health care (1–3). Studies of African American families with type 2 diabetes (4) or diabetic nephropathy (5) have revealed clustering of both diseases, indicating a genetic component to susceptibility. Genome scans in families have supported a genetic contribution to susceptibility to type 2 diabetes and diabetic nephropathy in African Americans (4,6).Plasma adiponectin levels are inversely correlated with diabetes and insulin resistance (7,8). In contrast, plasma adiponectin has been shown to be increased in patients with kidney disease (9), and studies suggest that increased adiponectin concentration is a predictor of subsequent kidney disease (10).Adiponectin gene (ADIPOQ) polymorphisms have been implicated in type 2 diabetes (11) and type 1 diabetic nephropathy (12,13). Few studies have addressed genetic variants in adiponectin and association with diabetes in Africans (14) or African Americans (15). This second report in African Americans noted several differences between European-derived samples and African Americans regarding associations between ADIPOQ polymorphisms and body composition and lipid phenotypes highlighting potential ethnic differences in the adiponectin gene and the importance of investigating variants in this gene in African Americans.Given the paucity of studies on adiponectin gene polymorphisms and type 2 diabetes or diabetic nephropathy in African Americans and the high risk of these diseases in this population, a thorough interrogation of this gene in African Americans was warranted. We tested 24 single-nucleotide polymorphisms (SNPs) in the adiponectin gene for association with type 2 diabetes and diabetic nephropathy in a large collection of African Americans residing in the southeastern U.S.