Document Type : Original Article
Authors
1
Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
2
Department of Modern Science and Technologies; and Biochemistry of Nutrition Research Center; School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3
Division of Applied Medicine, Medical School, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
4
Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
5
VU University Medical Center, Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
6
University of Bologna, Bologna, Italy
7
Peter MacCallum Centre, St Andrew's Place, Melbourne, Australia
8
Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH, UK
Abstract
Metabolic syndrome (MetS) is characterized by a cluster of cardiovascular risk factors that include: abdominal obesity, dyslipidaemia, hypertension, insulin resistance and impaired glucose tolerance. Recent genome wide association studies have identified several susceptibility regions involved in lipid metabolism that are also associated with MetS. We have explored the association of 9 genetic polymorphisms involved in lipid metabolism and hypertension, including: MTHFR C677T, SELE L554F, FGB - 455G>A, GNB3 C825T, ZNF259 C>G, PSRC-1 A>G, CETP I405V, LPL S447X and LPA C>T in 97 subjects with MetS and 96 individuals without MetS who were recruited randomly from Mashhad stroke and heart atherosclerotic disorder (MASHAD) study using a stratified cluster random sampling technique. Anthropometric parameters and biochemical measurements were determined in all the subjects. Genotyping was carried out followed by univariate and multivariate analyses. The subjects with MetS had a higher triglyceride and lower HDL- C. CG+ GG genotypes of ZNF259 polymorphism (rs964184 C>G) and TT+CT genotypes of MTHFR C677T (rs1801133) were associated with MetS, and individuals carrying the G allele for ZNF259 or the T allele for MTHFR polymorphisms were associated with MetS (e.g, odds ratio (OR) for CG+GG genotypes vs. CC wild type: 2.52, CI=1.33-4.77; P=0.005). However, after multiple comparison adjustment, this relationship remained significant only for CG+ GG genotypes of ZNF259 polymorphism. Moreover, the ZNF259 CG+ GG genotypes were associated with increased serum concentrations of triglycerides and LDL-C, compared to the wild type. These data support the necessity for further studies in larger multicenter settings.
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