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J Appl Physiol 105: 859-867, 2008. First published July 17, 2008; doi:10.1152/japplphysiol.90655.2008
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TNF promoter polymorphisms associated with muscle phenotypes in humans

Dongmei Liu,1 E. Jeffrey Metter,2 Luigi Ferrucci,2 and Stephen M. Roth1

1Department of Kinesiology, School of Public Health, University of Maryland, College Park; and 2Clinical Research Branch, National Institute on Aging, Harbor Hospital, Baltimore, Maryland

Submitted 15 May 2008 ; accepted in final form 17 July 2008

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/m2) 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-{alpha}


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{at}umd.edu)






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