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

Authors Fu L, Li Y, Luo D, Deng S, Hu YQ

Received 14 February 2019

Accepted for publication 31 May 2019

Published 23 July 2019 Volume 2019:12 Pages 1201—1212


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Muthuswamy Balasubramanyam

Liwan Fu,1 Ya-nan Li,1 Dongmei Luo,1,2 Shufang Deng,1 Yue-Qing Hu1,3

1State Key Laboratory of Genetic Engineering, Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 2Department of Information and Computing Science, School of Mathematics and Physics, Anhui University of Technology, Maanshan, Anhui, People’s Republic of China; 3Shanghai Center for Mathematical Sciences, Fudan University, Shanghai, People’s Republic of China

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: homocysteine, MTHFR, obesity, polymorphism

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