Evidence on the causal link between homocysteine and hypertension from a meta-analysis of 40 173 individuals implementing Mendelian randomization

Numerous researchers have investigated the associations among methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism, homocysteine (Hcy) concentration, and hypertension. However, the results are controversial. Thus, a meta-analysis implementing Mendelian randomization approach was conducted to examine the hypothesis that elevated Hcy concentration plausibly contributes to increased risk of hypertension. Based on several inclusion and exclusion criteria, eligible studies were selected to explore the correlation between MTHFR C677T and hypertension risk, MTHFR C677T and Hcy concentration in hypertension, and Hcy concentration and hypertension, and they were evaluated by odds ratios (ORs), effect size (ES), and standard mean difference with their corresponding 95% confidence intervals (95% CIs), respectively. Moreover, Mendelian randomization was implemented to evaluate the relationship between Hcy and hypertension. Consequently, 14 378 cases and 25 795 controls were involved in this study and the results showed that MTHFR C677T led to an elevated risk of hypertension (for T vs C: OR = 1.27, 95% CI = 1.17-1.37; for TT vs CC: OR = 1.53, 95% CI = 1.30-1.79). Additionally, in hypertensive subjects, the pooled Hcy concentration in individuals of TT genotype was 7.74 mu mol/L (95% CI: 5.25-10.23) greater than that in individuals of CC genotype. Moreover, the pooled Hcy concentration in hypertensive was 0.69 mu mol/L (95% CI: 0.50-0.87) greater than that in controls. The estimated causal OR associated with hypertension was 1.32 for 5 mu mol/L Hcy increment. Via MTHFR C677T polymorphism, the findings in the present study demonstrated that there exists evidence on causal link between Hcy concentration and the risk of hypertension.