Association of Human Fetuin-A rs4917 Polymorphism With Obesity in 2 Cohorts

Background: Previous studies have shown association of the multifunctional hepatic protein alpha 2HS-glycoprotein/human fetuin A with insulin resistance, type 2 diabetes mellitus, metabolic syndrome, obesity, and atherosclerosis. Reports of contribution of alpha 2HS-glycoprotein/human fetuin A rs4917 single-nucleotide polymorphism to the development of these pathologic processes are inconsistent. We aimed to investigate the association between variants of rs4917 and parameters of obesity, lipid status, the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha), adipokines (adiponectin, resistin), and insulin resistance in 2 cohorts. Methods: Eighty-one healthy persons (cohort 1) and 157 patients with previous myocardial infarction (cohort 2) were included in this cross-sectional study. rs4917 Polymorphism was determined by the allele-specific KASP by design genotyping assays. Results: In cohort 1, T-nucleotide carriers had lower low-density lipoprotein cholesterol levels compared with non-T carriers. The serum concentration of TNF-alpha was found to be higher carrying the non-T allele in cohort 1; however, this difference was not observed in cohort 2. In cohort 2, T carriers had lower body mass index and abdominal and waist circumferences than did non-T carriers. The T nucleotide was more frequent in nonobese than in obese patients (chi(2) = 5.217, P = 0.022). Nonobese, nondiabetic T carriers still had lower body mass index and waist circumference than did non-T carriers. Conclusions: Our data suggest that the T nucleotide in rs4917 is associated with more favorable lipid status among healthy persons (i.e., lower low-density lipoprotein cholesterol) and anthropologic parameters of obesity in cohort 2. The protective role of the T allele may also be associated with lower TNF-alpha levels found in healthy individuals.