Associations of MTHFR C677T and MTRR A66G Gene Polymorphisms with Metabolic Syndrome: A Case-Control Study in Northern China

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.

Gender-specific interactions of MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on serum lipid levels in a Chinese Han population

“…The gender-specific effect of the MTRR A66G polymorphism on blood lipid profiles was not well explored. Moreover, unlike our study selecting general population without any severe diseases, the studies mentioned above were conducted in specific populations with various disorders such as hypertension [11, 42], metabolic syndrome [44] and schizophrenia [45], which may be a crucial contributor for the difference between our results and the prior findings.…”

“…But in another sample of Chinese hypertensive patients, a marginally significant association was found between MTRR 66GG genotype and elevated serum TC levels [42]. Our group previously conducted a case-control study to investigate the association of this genetic variant with metabolic syndrome [44], and found that MTRR 66GG genotype was associated with increased risk of high TG (TG ≥ 1.7 mmol/L), while no significant relationship was detected between this polymorphism and low HDL-C (HDL-C < 1.03 mmol/L for males and < 1.30 mmol/L for females). However, Misiak et al found there was no significant relationship between this polymorphism and TG or HDL-C levels in both first-episode schizophrenia patients and healthy controls [45].…”

An Association Study Between Gene Polymorphisms of Folic Acid Metabolism Enzymes and Biochemical and Hormonal Parameters in Acromegaly

“…MTRR is a flavoprotein, which plays a regulatory role in the homocysteine metabolic pathway by maintaining MTR in an active state in homocysteine metabolism (Sharp and Little, 2004;Hong et al, 2013). There are several reports revealing that MTRR A66G and MTR A2576G gene polymorphisms cause reduced enzymatic activity of the MTRR and MTR enzymes (Paisley et al, 2011;Rai et al, 2013;Yang et al, 2013;Yang et al, 2014).…”

Mutations in the MTHFR gene and their associations with milk production traits in dairy goats

“…A genetic variant with a C to T substitution at position 677 in the MTHFR gene leads to an amino acid change from alanine to valine, thereby yielding a thermolabile variant of the enzyme with reduced activity and elevated plasma homocysteine levels (Frosst et al, 1995;Yang et al, 2014a). Alterations in the activity of MTHFR may influence the pathogenesis of conditions such as depression and schizophrenia by hindering 1-carbon metabolism (Frankenburg, 2007).…”