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Association of Human Fetuin-A rs4917 Polymorphism With Obesity in 2 Cohorts
  1. György Temesszentandrási, MD*,
  2. Krisztián Vörös, MD,
  3. Zoltán Böröcz, MD*,
  4. Edit Kaszás, MD,
  5. Zoltán Prohászka, MD, DSc,
  6. András Falus, DSc,
  7. Károly Cseh, MD, DSc‡¶,
  8. László Kalabay, MD, PhD
  1. From the *3rd Department of Internal Medicine and †Department of Family Medicine, Semmelweis University, ‡Károlyi Sándor Municipal Hospital; §Atherosclerosis Research Group of Hungarian Academy of Sciences; and Departments of ∥Genetics and Immunology, and Cell Sciences and ¶Public Health, Semmelweis University, Budapest, Hungary.
  1. Received May 29, 2014, and in revised form December 13, 2014.
  2. Accepted for publication December 18, 2014.
  3. Reprints: László Kalabay, MD, PhD, Department of Family Medicine, Semmelweis University, Kútvölgyi str. 4, Budapest, Hungary H-1125. E-mail: kalabay.laszlo{at}med.semmelweis-univ.hu.
  4. Authors’ contributions: G.T.: patient care and data collection; preparation of the manuscript; K.V.: preparation of the manuscript, literature research; Z.B.: data collection; Z.P.: determination of AHSG concentrations; critical review of the manuscript; A.F.: Member of the Hungarian Academy of Sciences: overview AHSG genotypization, critical review of the manuscript; E.K.: patient care and data collection; K.C.: study design, determination of adipokine concentrations, critical review of the manuscript; L.K.: conceived the idea of the study, critical review of the manuscript, statistical analysis, funds collection.
  5. The study was approved by the local Ethics Committee of the Károlyi Sándor Municipality Hospital.
  6. All persons gave their informed consent prior to their inclusion in the study.
  7. This work was supported by grant of the Hungarian Ministry of Health ETT 368/2009.
  8. The authors declare that they have no conflicts of interest to declare.

Abstract

Background Previous studies have shown association of the multifunctional hepatic protein α2HS-glycoprotein/human fetuin A with insulin resistance, type 2 diabetes mellitus, metabolic syndrome, obesity, and atherosclerosis. Reports of contribution of α2HS-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 α (TNF-α), 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-α 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 (χ2 = 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-α levels found in healthy individuals.

Key Words
  • α2HS-glycoprotein/fetuin A
  • rs4917
  • obesity
  • diabetes mellitus
  • myocardial infarction

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