Liu Dongmei, Metter E Jeffrey, Ferrucci Luigi, Roth Stephen M
Dept. of Kinesiology, Univ. of Maryland, College Park, MD 20742-2611, USA.
J Appl Physiol (1985). 2008 Sep;105(3):859-67. doi: 10.1152/japplphysiol.90655.2008. Epub 2008 Jul 17.
Tumor necrosis factor-alpha (TNF-alpha) is a potent catabolic factor to skeletal muscle. Single-nucleotide polymorphisms (SNPs) in the promoter region of the TNF-alpha coding gene, TNF, have been implicated in the interindividual variation in TNF-alpha production via transcriptional regulation. The present study investigated the association of muscle phenotypes with five TNF promoter SNPs, which potentially have biological significance. Female and male volunteers (n = 1,050) from the Baltimore Longitudinal Study of Aging were genotyped, and their regional and total body muscle mass, and arm and leg muscle strength were measured. Results indicated that putative high-expression alleles at positions -1031 and -863, individually or in combination in the haplotype 1031C-863A-857C-308G-238G, were associated with lower muscle mass in men. Specifically, carriers of -1031C, compared with noncarriers, exhibited lower arm muscle mass (6.4 +/- 0.1 vs. 6.8 +/- 0.1 kg, P = 0.01) and appendicular skeletal muscle mass (ASM) (24.3 +/- 0.4 vs. 25.4 +/- 0.2 kg, P = 0.02), with leg muscle mass and the ASM index (ASMI; kg/m(2)) also tending to be lower (P = 0.06 and 0.07). Similarly, -863A allele carriers (linked with -1031), compared with noncarriers, exhibited lower arm muscle mass (6.4 +/- 0.1 vs. 6.8 +/- 0.1 kg, P = 0.04). Carriers of the haplotype 1031C-863A-857C-308G-238G, compared with noncarriers, exhibited lower arm muscle mass (6.3 +/- 0.2 vs. 6.8 +/- 0.1 kg, P < 0.01), trunk muscle mass (25.7 +/- 0.5 vs. 26.9 +/- 0.3 kg, P < 0.05), and ASM (24.1 +/- 0.5 vs. 25.3 +/- 0.2 kg, P < 0.025), with tendencies for lower leg muscle mass and ASMI (P = 0.07 and 0.08). Results indicate that genetic variation in the TNF locus may contribute to the interindividual variation in muscle phenotypes in men.
肿瘤坏死因子-α（TNF-α）是一种对骨骼肌具有强大分解代谢作用的因子。TNF-α编码基因TNF启动子区域的单核苷酸多态性（SNP），已被认为通过转录调控参与了个体间TNF-α产生的差异。本研究调查了5个TNF启动子SNP与肌肉表型的关联，这些SNP可能具有生物学意义。对巴尔的摩纵向衰老研究中的女性和男性志愿者（n = 1050）进行基因分型，并测量他们的局部和全身肌肉质量以及手臂和腿部肌肉力量。结果表明，位于-1031和-863位点的假定高表达等位基因，单独或在单倍型1031C-863A-857C-308G-238G中组合，与男性较低的肌肉质量相关。具体而言，-1031C携带者与非携带者相比，手臂肌肉质量较低（6.4±0.1 vs. 6.8±0.1 kg，P = 0.01）和附属骨骼肌质量（ASM）较低（24.3±0.4 vs. 25.4±0.2 kg，P = 0.02），腿部肌肉质量和ASM指数（ASMI；kg/m²）也有降低趋势（P = 0.06和0.07）。同样，-863A等位基因携带者（与-1031连锁）与非携带者相比，手臂肌肉质量较低（6.4±0.1 vs. 6.8±0.1 kg，P = 0.04）。单倍型1031C-863A-857C-308G-238G的携带者与非携带者相比，手臂肌肉质量较低（6.3±0.2 vs. 6.8±0.1 kg，P < 0.01），躯干肌肉质量较低（25.7±0.5 vs. 26.9±0.3 kg，P < 0.05），以及ASM较低（24.1±0.5 vs. 25.3±0.2 kg，P < 0.025），腿部肌肉质量和ASMI也有降低趋势（P = 0.07和0.08）。结果表明，TNF基因座的遗传变异可能导致男性肌肉表型的个体间差异。
