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 μmol/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 μmol/L (95% CI: 0.50‐0.87) greater than that in controls. The estimated causal OR associated with hypertension was 1.32 for 5 μmol/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.
Objective
Numerous studies have explored the role of methylenetetrahydrofolate reductase gene (
MTHFR
) C677T polymorphism and homocysteine (Hcy) concentration in obesity, but the results are inconsistent. Hence, we performed a meta-analysis implementing Mendelian randomization approach to test the assumption that the increased Hcy concentration is plausibly related to the elevated risk of obesity.
Methods
Eligible studies were selected based on several inclusion and exclusion criteria. Correlations between
MTHFR
C677T and obesity risk,
MTHFR
C677T and Hcy concentration in obesity, Hcy concentration, and obesity were estimated by ORs, effect size and standard mean difference with their corresponding 95% CIs, respectively. Furthermore, Mendelian randomization analysis was performed to estimate the relationship between Hcy level and obesity.
Results
Consequently, this meta-analysis implemented with Mendelian randomization approach was conducted among 8,622 cases and 29,695 controls. The results indicated that
MTHFR
C677T is associated with an increased risk of obesity (for T vs C: OR=1.06, 95% CI=1.02–1.10; for TT vs CC: OR=1.13, 95% CI=1.03–1.24). Moreover, in obese subjects, the pooled Hcy concentration in individuals of TT genotype was 2.91 mmol/L (95% CI: 0.27–5.55) higher than that in individuals of CC genotype. Furthermore, the pooled Hcy concentration in subjects with obesity was 0.74 mmol/L (95% CI: 0.36–1.12) higher than that in controls. The evaluated plausible OR associated with obesity was 1.23 for 5 μmol/L Hcy level increase.
Conclusions
Through this meta-analysis, we emphasize a strong relationship between Hcy level and obesity by virtue of
MTHFR
C677T polymorphism.
Many studies have investigated the association between Tumor necrosis factor-α-308 G>A (rs1800629) and the risk of esophageal cancer. However, their results are inconsistent. Therefore, we performed a meta-analysis of available data to investigate any possible association between this polymorphism and esophageal cancer risk. We searched PubMed, EMBASE, Web of Science, and the CNKI database for articles published up to 2016. Crude and adjusted odds ratio with 95% confidence intervals were calculated using fixed or random effects models. We used a dominant model (GA+AA vs GG), a recessive model (AA vs GG+GA), an over-dominant model (GG+AA vs GA), and allele frequency (G vs A) to identify any association. Eleven studies with 5617 participants were included in the meta-analysis. Our results suggest that TNF-α-308 G>A (rs1800629) is not significantly associated with a risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma. For genetic association studies, negative results of meta-analysis have a high level of evidence, and these results are important in this era of high-throughput sequencing-based precision medicine.
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