Genetic analysis of adiponectin and obesity in Hispanic families: the IRAS Family Study

Abstract

Adiponectin, coded for by the APM1 gene, is a novel adipocyte-derived hormone implicated in energy homeostasis and obesity. Several genetic studies have observed evidence of association between APM1 gene polymorphisms and features of the metabolic syndrome, such as insulin resistance and obesity. As part of a comprehensive genetic analysis of the APM1 gene, we have screened 96 unrelated individuals for polymorphisms in the promoter, coding regions, and 3'untranslated region (UTR). Three promoter single-nucleotide polymorphisms (SNPs), two rare coding SNPs (G113A and T1233C), and 13 SNPs in the 3'UTR were identified. Eighteen SNPs were genotyped in 811 Hispanic individuals from 45 families in the IRAS Family Study (IRASFS). SNPs were tested for association with six obesity quantitative traits (body mass index, waist, waist:hip ratio, subcutaneous adipose tissue, visceral adipose tissue, and visceral:subcutaneous ratio). Significant evidence of association to at least one of the obesity traits was identified in seven of the 18 SNPs (<0.001-0.05). The promoter SNP INS CA-11156 was the most consistently associated SNP and was associated significantly with all measures of obesity, except the visceral:subcutaneous ratio (P-values 0.009-0.03). Haplotype analysis supported this evidence of association, with haplotypes containing an insertion of one CA repeat at position -11156 consistently being associated with lower obesity values (P-value <0.001-0.05). The adiponectin polymorphisms, in particular those in the promoter region, thus show significant association with obesity measures in the Hispanic population. Additional studies are needed to confirm our findings and determine which polymorphism causes the functional effect.

Adiponectin Level and Gene Variability Are Obesity and Metabolic Syndrome Markers in a Young Population

“…In contrast, some other studies demonstrated that the common -11377C allele was strongly associated with obesity and MetS parameters (17,52). Our findings are also consistent with previous reports in different populations and different age groups (53,54,55) stating that ADIPOQ gene may play an important role in MetS. Results of these reports pointed that regional differences in body fat affected the risk of metabolic abnormalities, and also ADIPOQ gene variants were suggested as modulators of visceral fat accumulation.…”

Genetic mapping of a 17q chromosomal region linked to obesity phenotypes in the IRAS family study

“…It is important to note that all three obesity traits have a high degree of correlation in the IRASFS (rX0.70; 31 ). Linkage results reported here are adjusted for age, gender, and center, but not BMI.…”

Relation of a common variant of the adiponectin gene to serum adiponectin concentration and metabolic traits in an aged Japanese population

“…The 30 SNPs examined encompassed the genomic region (25 kbp) containing ADIPOQ exons and introns plus 8 kbp upstream and 1 kbp downstream (chromosome 3: genome positions 188034376-188059821) and were selected from those listed in the National Center for Biotechnology Information database dbSNP build 129 or those described in published studies. Several of the SNPs have previously been associated with adiponectin level 32 and metabolic disorders including obesity, 33,34 type II diabetes mellitus, 24,28 or cardiovascular disease. 25 In addition, we only selected SNPs for which the minor allele frequency (MAF) was shown to be 41% in Japanese subjects.…”