Associations of MTHFR C677T and MTRR A66G gene polymorphisms with metabolic syndrome: a case-control study in Northern China.

Boyi Yang,Yanxun Wang,Quanmei Zheng,Guifan Sun,Xueyuan Zhi,Jian Wei,Da Wang,Yongfang Li,Yinuo Wang,Shujun Fan

doi:10.3390/ijms151221687

Abstract

Prior evidence indicates that homocysteine plays a role in the development of metabolic syndrome (MetS). Methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms are common genetic determinants of homocysteine levels. To investigate the associations of the MTHFR C677T and MTRR A66G polymorphisms with MetS, 692 Chinese Han subjects with MetS and 878 controls were recruited. The component traits of MetS and the MTHFR C677T and MTRR A66G genotypes were determined. A significant association was observed between the MTHFR 677T allele and increased risk of MetS, high fasting blood glucose, high waist circumference, and increasing number of MetS components. The MTRR A66G polymorphism was associated with an increased risk of MetS when combined with the MTHFR 677TT genotype, although there was no association found between MetS and MTRR A66G alone. Furthermore, the MTRR 66GG genotype was associated with high fasting blood glucose and triglycerides. Our data suggest that the MTHFR 677T allele may contribute to an increased risk of MetS in the northern Chinese Han population. The MTRR A66G polymorphism is not associated with MetS. However, it may exacerbate the effect of the MTHFR C677T variant alone. Further large prospective population-based studies are required to confirm our findings.

Highlights

Metabolic syndrome (MetS) is characterized through a cluster of various metabolic abnormalities, including central obesity, dyslipidemia, elevated blood pressure (BP) and high glucose concentrations.Available evidence shows that the prevalence of MetS is rapidly increasing worldwide [1,2]
Significant differences existed between the two groups in body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels
We found that the Methylenetetrahydrofolate reductase (MTHFR) 677T allele carriers had an increased risk of MetS, and the 677TT genotype showed a significant correlation with high FBG, high WC, and having more MetS components, respectively

Summary

Introduction

Available evidence shows that the prevalence of MetS is rapidly increasing worldwide [1,2]. MetS and its individual components have been reported to be associated with increased risk of diabetes and cardiovascular diseases, as well as with high all-cause mortality [4,5,6]. Several studies have linked hyperhomocysteinemia (HHcy) to MetS and its individual components [7,8,9,10,11,12], and it has even been described as an integral component of MetS in rats [13]. Potential mechanisms linking HHcy with MetS and its components include promoting endothelial dysfunction, inducing insulin resistance, and influencing DNA methylation status [10,14,15,16,17]. Because of the relationship between Hcy and MetS, factors influencing the plasma Hcy levels may potentially relate to MetS

Results

Discussion

Conclusion