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Association of a polymorphic variant of the adiponectin gene with insulin resistance in african americans.

ABSTRACT: Hypertension, type 2 diabetes, and obesity are common complex disorders that contribute to cardiovascular (CV) disease. Insulin resistance increases CV risk and is present in these disorders. Adiponectin, a protein secreted by adipocytes with metabolic and vascular protective effects, is lower in obesity and insulin resistance. Several single nucleotide polymorphisms (SNP) have been identified in the adiponectin (ADIPOQ) gene. Associations of ADIPOQ polymorphisms with diabetes and obesity have been described in Caucasians and Asians. The purpose of this study was to determine if genetic variants of ADIPOQ are associated with insulin resistance and CV risk in African Americans. Metabolic traits (lipids, glucose, insulin, and insulin sensitivity) and blood pressure were measured in 273 African Americans. DNA was examined by DNA sequence analysis and SNPs of candidate genes including ADIPOQ were studied. Statistica analyses were performed by regression of the quantitative trait phenotypes on the groups defined by the SNP genotypes, adjusting for age, sex, and body mass index (BMI). SNP 712 (rs3774261) ofthe/lD/POQgene showed significant association with insulin resistance (p= 0.001). Despite the relatively small sample, our results indicate that genes that regulate adipocyte function may have a regulatory role in the expression of metabolic traits in obesity-associated chronic disease.

SUBMITTER: Specchia C

PROVIDER: S-EPMC5350656 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Association of a polymorphic variant of the adiponectin gene with insulin resistance in african americans.

Specchia Claudia C Scott Kathryn K Fortina Paolo P Devoto Marcella M Falkner Bonita B

Clinical and translational science 20081201 3

Hypertension, type 2 diabetes, and obesity are common complex disorders that contribute to cardiovascular (CV) disease. Insulin resistance increases CV risk and is present in these disorders. Adiponectin, a protein secreted by adipocytes with metabolic and vascular protective effects, is lower in obesity and insulin resistance. Several single nucleotide polymorphisms (SNP) have been identified in the adiponectin (ADIPOQ) gene. Associations of ADIPOQ polymorphisms with diabetes and obesity have b ...[more]

PMID: 20443850

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Project description:BackgroundAfrican Americans have a high risk for type 2 diabetes (T2D) and insulin resistance. Studies among other population groups have identified DNA methylation loci associated with insulin resistance, but data in African Americans are lacking. Using DNA methylation profiles of blood samples obtained from the Illumina Infinium® HumanMethylation450 BeadChip, we performed an epigenome-wide association study to identify DNA methylation loci associated with insulin resistance among 136 non-diabetic, unrelated African American men (mean age 41.6 years) from the Howard University Family Study.ResultsWe identified three differentially methylated positions (DMPs) for homeostatic model assessment of insulin resistance (HOMA-IR) at 5% FDR. One DMP (cg14013695, HOXA5) is a known locus among Mexican Americans, while the other two DMPs are novel-cg00456326 (OSR1; beta = 0.027) and cg20259981 (ST18; beta = 0.010). Although the cg00456326 DMP is novel, the OSR1 gene has previously been found associated with both insulin resistance and T2D in Europeans. The genes HOXA5 and ST18 have been implicated in biological processes relevant to insulin resistance. Differential methylation at the significant HOXA5 and OSR1 DMPs is associated with differences in gene expression in the iMETHYL database. Analysis of differentially methylated regions (DMRs) did not identify any epigenome-wide DMRs for HOMA-IR. We tested transferability of HOMA-IR associated DMPs from five previous EWAS in Mexican Americans, Indian Asians, Europeans, and European ancestry Americans. Out of the 730 previously reported HOMA-IR DMPs, 47 (6.4%) were associated with HOMA-IR in this cohort of African Americans.ConclusionsThe findings from our study suggest substantial differences in DNA methylation patterns associated with insulin resistance across populations. Two of the DMPs we identified in African Americans have not been reported in other populations, and we found low transferability of HOMA-IR DMPs reported in other populations in African Americans. More work in African-ancestry populations is needed to confirm our findings as well as functional analyses to understand how such DNA methylation alterations contribute to T2D pathology.

Dataset Information

Association of a polymorphic variant of the adiponectin gene with insulin resistance in african americans.

Publications

Association of a polymorphic variant of the adiponectin gene with insulin resistance in african americans.

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