Interactions Between Noncontigous Haplotypes in the Adiponectin Gene ACDC Are Associated With Plasma Adiponectin

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Diabetes (Impact Factor: 8.1). 03/2006; 55(2):523-9. DOI: 10.2337/diabetes.55.02.06.db05-0446
Source: PubMed


Adiponectin, an adipocyte protein important in insulin sensitization and cardioprotection, has a strong genetic component. We hypothesized that variants in the adiponectin gene (adipocyte collagen-domain containing [ACDC]) contribute to adiponectin levels in a biracial adolescent cohort. We genotyped 11 ACDC single nucleotide polymorphisms (SNPs) in 631 non-Hispanic white and 553 African-American unrelated adolescents in grades 5-12 randomly selected from the Princeton School District Study. ACDC SNPs -11,391 (A allele), -10,068 (G allele), and +276 (T allele) were associated with higher adiponectin, adjusting for sex, puberty stage, BMI Z score, and waist Z score. Contiguous two-SNP haplotypes of promoter variants -11,391/-10,068 were significantly associated with adiponectin levels in whites and African Americans (P < 0.0001 and 0.03, respectively). Extended haplotypes from the promoter through the second intron (-11,391 to +349) strongly associated with adiponectin in whites (P = 6 x 10(-11)) and African Americans (P = 0.004), but haplotypes of first intron SNPs -4,521 to -657 did not (P > 0.2). Noncontiguous haplotypes or interactions between two-SNP (-11,391/-10,068) and three-SNP (+45, +276, and +349) haplotypes predicted adiponectin better than either region alone. Variants of ACDC are associated with adiponectin levels in whites and African Americans. Interactions between noncontiguous ACDC haplotypes strongly influence adiponectin levels, suggesting nonadditive and potentially cis relationships between these regions.

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Available from: Lisa J Martin, Aug 31, 2015
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    • "In German and North America subjects, SNP +45 is associated with diabetes and IR; in French subjects, c.11377 and c.11391 SNPs are significantly associated with low levels of adiponectin and T2DM; in Italy, c.11377 SNP resulted to be correlated to adiponectin levels in severe obese patients [43, 47, 78]. Recently, haplotype analysis in 631 non-Hispanic white and 553 African-American subjects identified a strong link between noncontiguous ACDC haplotypes and adiponectin levels [79]. "
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