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

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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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Acknowledgments

This work was partially funded by NIH (R01 AR050496, K01 AR02170-01, R01 AR45349-01, R01 GM60402-01A1, R21 AG027110-01A1 and R01 AG026564-01A2), and an LB595 grant from the State of Nebraska. The study benefited from National Science Foundation of China (30570875), Huo YingDong Education Foundation, Hunan Province, Xi’an Jiaotong University and the Ministry of Education of China. Xiaogang Liu was partially supported by Doctoral Foundation of Xi’an Jiaotong University (DFXJTU2004-11).

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Authors and Affiliations

  1. The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an Shaanxi, 710049, People’s Republic of China

    Xiaogang Liu & Hong-Wen Deng

  2. Departments of Orthopedic Surgery and Basic Medical Sciences, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA

    Xiaogang Liu, Lan-Juan Zhao, Yong-Jun Liu & Hong-Wen Deng

  3. Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, NE, 68131, USA

    Dong-Hai Xiong & Robert R. Recker

  4. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha Hunan, 410081, People’s Republic of China

    Hong-Wen Deng

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  1. Xiaogang Liu
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Correspondence to Hong-Wen Deng.

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Liu, X., Zhao, LJ., Liu, YJ. et al. The MTHFR gene polymorphism is associated with lean body mass but not fat body mass. Hum Genet 123, 189–196 (2008). https://doi.org/10.1007/s00439-007-0463-7

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