TNF Promoter Polymorphisms Associated with Muscle Phenotypes i...

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 inter-individual variation in TNF-alpha 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/m(2)) 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. Key words: genetics, inflammation, cytokine, skeletal muscle.