The MTHFR gene polymorphism is associated with lean body mass but not fat body mass

Hum Genet. 2008 Mar;123(2):189-96. doi: 10.1007/s00439-007-0463-7. Epub 2008 Jan 8.


Along with aging, human body composition undergoes notable changes and may incur sarcopenia, obesity or osteoporosis. Sarcopenia is related to a wide series of human health problems and can be largely characterized by loss of lean body mass (LBM). Studies have showed relevance of methylenetetrahydrofolate reductase (MTHFR) with variation in LBM and fat body mass (FBM). To test if polymorphism of the MTHFR gene is underlying the pathology of sarcopenia and obesity, we concurrently tested five single nucleotide polymorphisms (SNPs) of the MTHFR gene for association with LBM, FBM and body mass index (BMI) in 405 Caucasian nuclear families comprising 1,873 individuals. After correction for multiple testing, we detected significant associations for LBM with rs2066470 (P = 0.0006), rs4846048 (P = 0.0007) and with rs3737964 (P = 0.004), as well as for BMI with rs4846048 (P = 0.009). Polymorphism of rs2066470 explains 3.67% of LBM variation in this sample. The association between BMI and rs4846048 diminished after adjusting for LBM, suggesting that the association between BMI and rs4846048 is largely due to LBM instead of the fat component. In concert, no significant associations were identified for FBM with any of the studied SNPs. The results of single-locus association analyses were corroborated by haplotype-based analyses. In summary, the MTHFR gene polymorphism is associated with LBM, suggesting that MTHFR may play an important role in LBM variation. In addition, the MTHFR gene polymorphism is not associated with FBM or obesity in this sample.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / physiology*
  • Adult
  • Body Composition / genetics*
  • Body Mass Index
  • Body Weight / genetics*
  • Female
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Middle Aged
  • Obesity / etiology
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*


  • Methylenetetrahydrofolate Reductase (NADPH2)