Liu Xiaogang, Zhao Lan-Juan, Liu Yong-Jun, Xiong Dong-Hai, Recker Robert R, Deng Hong-Wen
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.
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.
随着年龄增长，人体成分会发生显著变化，并可能引发肌肉减少症、肥胖症或骨质疏松症。肌肉减少症与一系列人类健康问题相关，其主要特征是去脂体重（LBM）的丧失。研究表明，亚甲基四氢叶酸还原酶（MTHFR）与LBM和脂肪体重（FBM）的变化有关。为了检验MTHFR基因多态性是否是肌肉减少症和肥胖症病理的基础，我们在由1873名个体组成的405个白种人核心家庭中，同时检测了MTHFR基因的五个单核苷酸多态性（SNP）与LBM、FBM和体重指数（BMI）的关联。经过多重检验校正后，我们发现LBM与rs2066470（P = 0.0006）、rs4846048（P = 0.0007）以及rs3737964（P = 0.004）存在显著关联，BMI与rs4846048（P = 0.009）存在显著关联。rs2066470的多态性解释了该样本中LBM变异的3.67%。调整LBM后，BMI与rs4846048之间的关联减弱，这表明BMI与rs4846048之间的关联主要归因于LBM而非脂肪成分。同时，未发现FBM与任何研究的SNP存在显著关联。单基因座关联分析的结果得到了基于单倍型分析的证实。总之，MTHFR基因多态性与LBM相关，表明MTHFR可能在LBM变异中起重要作用。此外，在该样本中，MTHFR基因多态性与FBM或肥胖症无关。
