Associations of the MTHFR rs1801133 polymorphism with coronary artery disease and lipid levels: a systematic review and updated meta-analysis

Zhi Luo,Yongyan Song,Irfan Muhammad,Zhan Lu,Jiaojiao Zhang,Yun Chen,Qiuhong Chen

doi:10.1186/s12944-018-0837-y

Abstract

BackgroundThe associations of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) rs1801133 polymorphism with coronary artery disease (CAD) and plasma lipid levels have been widely investigated, but the results were inconsistent and inconclusive. This meta-analysis aimed to clarify the relationships of the rs1801133 polymorphism with CAD and plasma lipid levels.MethodsBy searching in PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang, VIP and CNKI databases, 123 studies (87,020 subjects) and 65 studies (85,554 subjects) were identified for the CAD association analysis and the lipid association analysis, respectively. Odds ratio (OR) and standardized mean difference (SMD) were used to determine the effects of the rs1801133 polymorphism on CAD risk and lipid levels, respectively.ResultsThe variant T allele of the rs1801133 polymorphism was associated with increased risk of CAD under allelic model [OR = 1.11, 95% confidence interval (CI) = 1.06–1.17, P < 0.01], additive model (OR = 1.25, 95% CI = 1.14–1.37, P < 0.01), dominant model (OR = 1.11, 95% CI = 1.04–1.17, P < 0.01), and recessive model (OR = 1.22, 95% CI = 1.12–1.32, P < 0.01). The T carriers had higher levels of total cholesterol (TC) (SMD = 0.04, 95% CI = 0.01–0.07, P = 0.02) and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.07, 95% CI = 0.01–0.12, P = 0.01) than the non-carriers.ConclusionsThe meta-analysis suggested that the T allele of the rs1801133 polymorphism is a risk factor for CAD, which is possibly and partly mediated by abnormal lipid levels.

Highlights

The associations of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) rs1801133 polymorphism with coronary artery disease (CAD) and plasma lipid levels have been widely investigated, but the results were inconsistent and inconclusive
Association of the r1801133 polymorphism with CAD The variant T allele of the rs1801133 polymorphism was associated with increased risk of CAD under allelic model [odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.06–1.17, P < 0.01], additive model (OR = 1.25, 95% CI = 1.14–1.37, P < 0.01), dominant model (OR = 1.11, 95% CI = 1.04–1.17, P < 0.01) and recessive model (OR = 1.22, 95% CI = 1.12–1.32, P < 0.01) (Table 1)
MTHFR 5,10-methylenetetrahydrofolate reductase gene, SMD standardized mean difference, 95% CI 95% confidence interval, HWE Hardy-Weinberg equilibrium, TG triglyceride, TC total cholesterol, LDL-C low-density lipoprotein cholesterol, highdensity lipoprotein cholesterol (HDL-C) high-density lipoprotein cholesterol, CAD coronary artery disease, T2DM type 2 diabetes mellitus of TC (SMD = 0.01, 95% CI = − 0.00-0.03, Pheterogeneity = 0.38, PSMD = 0.15) and HDL-C (SMD = − 0.02, 95% CI = − 0.03--0.00, Pheterogeneity = 0.48, PSMD = 0.05) changed significantly after excluding these outlier comparisons (Table 4)

Summary

Introduction

The associations of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) rs1801133 polymorphism with coronary artery disease (CAD) and plasma lipid levels have been widely investigated, but the results were inconsistent and inconclusive. This meta-analysis aimed to clarify the relationships of the rs1801133 polymorphism with CAD and plasma lipid levels. The activated methyl group of SAM can be transferred to target substrates such as DNA under the catalysis of methyltransferase, and SAM itself is converted into S-adenosine homocysteine after demethylation. Homocysteine accepts the methyl group from 5-MTHF and methionine is formed again

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