Plausible relationship between homocysteine and obesity risk via MTHFR gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization - PubMed (original) (raw)

Plausible relationship between homocysteine and obesity risk via MTHFR gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization

Liwan Fu et al. Diabetes Metab Syndr Obes. 2019.

Abstract

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.

Keywords: MTHFR; homocysteine; obesity; polymorphism.

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Conflict of interest statement

The authors report no conflicts of interests in this work.

Figures

Figure 1

Figure 1

PRISMA flow diagram for selection of studies in the meta-analysis.

Figure 2

Figure 2

Forest plot of the evaluation for the effect size (ES) in Hcy level between the MTHFR genotypes (TT vs CC) in obese patients.

Figure 3

Figure 3

Forest plot of the evaluation for the effect size (ES) in Hcy level between the MTHFR genotypes (TT vs CT) in obese patients.

Figure 4

Figure 4

Forest plot of the MTHFR C677T associated with obesity risk (under homozygous codominant model: TT vs CC). Abbreviations: BWHHS, british women’s heart and health study; ALSPAC, avon longitudinal study of parents and children women cohort study; CCHS, copenhagen city heart study.

Figure 5

Figure 5

Forest plot of the MTHFR C677T associated with obesity risk (under allelic model: T vs C). Abbreviations: BWHHS, british women’s heart and health study; ALSPAC, avon longitudinal study of parents and children women cohort study; CCHS, copenhagen city heart study.

Figure 6

Figure 6

Forest plot of standardized mean difference (SMD) in Hcy levels between obese patients and control subjects in included studies.

Figure 7

Figure 7

Forest plot of standardized mean difference (SMD) in Hcy levels between obese patients and control subjects in included studies.

Comment in

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