Tuesday, February 12, 2008

MTHFR - the gene with the big, bad name - association with lean body mass

I posted about this gene a while back in reference not only to its' funny name but also to the hypothesized selection pressures that created a north-south gradient in Europe for one of its SNPs (677T - rs1801133), related to its' purported link to folate metabolism, and specifically, pregnancy loss (as well as a bunch of other conditions) due to hyperhomocysteinemia. (Here is the link to that paper).
Apparently, variants in this gene are also associated with variation in BMI and LBM (lean body mass). In this new paper (see below) the authors look for assocations between BMI and LBM and 5 SNPs in the MTHFR gene, in a "caucasian" population. None of the SNPs in this study is the same as the one mentioned above. From the intro:
Epidemiological studies found that plasma homocysteine was correlated with LBM (Rauh et al. 2001) and BMI (Jacques et al. 2001).
This MTHFR seems to be a gene with far reaching implications!

The MTHFR gene polymorphism is associated with lean body mass but not fat body mass
Xiaogang Liu, Lan-Juan Zhao, Yong-Jun Liu, Dong-Hai Xiong, Robert R. Recker and Hong-Wen Deng
Human Genetics Early online
Abstract 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.

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