Abstract
Several studies have examined the associations of methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with being overweight/obesity. However, the results are still controversial. We therefore conducted a case-control study (517 cases and 741 controls) in a Chinese Han population and then performed a meta-analysis by combining previous studies (5431 cases and 24,896 controls). In our case-control study, the MTHFR C677T polymorphism was not significantly associated with being overweight/obesity when examining homozygous codominant, heterozygous codominant, dominant, recessive and allelic genetic models. The following meta-analysis confirmed our case-control results. Heterogeneity was minimal in the overall analysis, and sensitivity analyses and publication bias tests indicated that the meta-analytic results were reliable. Similarly, both the case-control study and meta-analysis found no significant association between the MTRR A66G polymorphism and being overweight/obesity. However, sensitivity analyses showed that the associations between the MTRR A66G polymorphism and being overweight/obesity became significant in the dominant, heterozygous codominant and allelic models after excluding our case-control study. The results from our case-control study and meta-analysis suggest that both of the two polymorphisms are not associated with being overweight/obesity. Further large-scale population-based studies, especially for the MTRR A66G polymorphism, are still needed to confirm or refute our findings.
Highlights
Being overweight/obesity has become a serious public health problem worldwide, which could increase the likelihood of many diseases, such as diabetes mellitus, cardiovascular diseases and some cancers [1]
Because the average age of the overweight/obesity subjects was greater than that of normal subjects and the sex was not matched between the two groups, clinical data were analyzed using analysis of covariance with age and sex as covariates
For the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, the genotype distribution in the control group was consistent with Hardy–Weinberg equilibrium (HWE) (p = 0.662)
Summary
Being overweight/obesity has become a serious public health problem worldwide, which could increase the likelihood of many diseases, such as diabetes mellitus, cardiovascular diseases and some cancers [1]. Several epidemiological studies have reported higher homocysteine or lower folate levels in overweight/obesity subjects compared with normal weight controls [18,19,20]. The mechanisms underlying these observations remain unclear; some investigators have postulated that elevated homocysteine levels might affect the development of being overweight/obesity via epigenetic control of gene expression in the regulation of body fat storage, because the methyl group and homocysteine metabolism are interrelated processes and are closely related to methylation of DNA and of amino acid residues on histones [5,6,21,22]. Recent data from animal experiments, cell studies and genetic studies seem to support this hypothesis [23,24,25]
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