Tumor necrosis factor-α (TNF-α) is a potent catabolic factor to skeletal muscle. Single-nucleotide polymorphisms (SNPs) in the promoter region of the TNF-α coding gene, TNF , have been implicated in the interindividual variation in TNF-α 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. genetics; skeletal muscle; inflammation; cytokine; tumor necrosis factor-α Address for reprint requests and other correspondence: S. M. Roth, 2134 SPH Bldg., Dept. of Kinesiology, School of Public Health, Univ. of Maryland, College Park, MD 20742-2611 (e-mail: sroth1@umd.edu )
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TNF promoter polymorphisms associated with muscle phenotypes in humans
Liu, Dongmei; Metter, E. Jeffrey; Ferrucci, Luigi; Roth, Stephen M.
Follow Journal of Applied Physiology
, Volume 105 (3): 859
The American Physiological Society – Sep 1, 2008
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