Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk? From a Case-Control to a Meta-Analysis of 30,327 Subjects

Int J Mol Sci. 2015 May 26;16(6):11849-63. doi: 10.3390/ijms160611849.

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.

Keywords: MTHFR; MTRR; obesity; overweight; polymorphism.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Asian People / genetics*
  • Case-Control Studies
  • China
  • Female
  • Ferredoxin-NADP Reductase / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Obesity / genetics*
  • Overweight / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)