Submitted on May 15, 2008
Revised on July 3, 2008
Accepted on July 17, 2008
TNF Promoter Polymorphisms Associated with Muscle Phenotypes in Humans
Dongmei Liu1, E. Jeffrey Metter, Luigi Ferrucci, and Stephen M Roth1*
1 University of Maryland
* To whom correspondence should be addressed. E-mail: sroth1{at}umd.edu.
Tumor necrosis factor alpha (TNF-
) is a potent catabolic factor to skeletal muscle. Single nucleotide polymorphisms (SNPs) in the promoter region of the TNF- coding gene, TNF, have been implicated in the inter-individual variation in TNF- production via transcriptional regulation. The present study investigated the association of muscle phenotypes with 5 TNF promoter SNPs, which potentially have biological significance. Female and male volunteers (n=1050) 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 males. Specifically, carriers of -1031C, compared with non-carriers, exhibited lower arm muscle mass (6.4±0.1 vs. 6.8±0.1kg, p=0.01) and appendicular skeletal muscle mass (ASM) (24.3±0.4 vs. 25.4±0.2kg, 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 non-carriers, exhibited lower arm muscle mass (6.4±0.1 vs. 6.8±0.1kg, p=0.04). Carriers of the haplotype '1031C-863A-857C-308G-238G', compared with non-carriers, exhibited lower arm muscle mass (6.3±0.2 vs. 6.8±0.1kg, 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±0.2kg, 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 inter-individual variation in muscle phenotypes in men.
