TNFα‐308G/A Genotype is Associated with Muscle Mass in Humans

Abstract

PURPOSE: Tumor necrosis factor alpha (TNFa) has been implicated in the regulation of muscle protein metabolism. A promoter polymorphism in the TNFa gene (TNFa −308 G/A) has been associated with higher production of TNFa. In this study, the relationship between TNFa −308G/A genotype and muscle mass was investigated in adult individuals. METHODS: 1095 participants of Baltimore Longitudinal Study of Aging (BLSA) (age range: 19 to 97 yr, 529 females and 566 males) were genotyped for TNFa −308G/A. Skeletal muscle mass (measured by DXA) was compared among different genotype groups. Age, gender, race and height were accounted for as confounding factors. RESULTS: TNFa genotype was significantly associated with both total body lean mass (LM) (p<0.0001) and appendicular skeletal muscle mass (ASMM) (p=0.0021). The AA genotype group (n=28) had higher muscle mass than the GA and GG groups (n=306 and 760) (LM: 68.1±2.2 vs. 56.2±0.6 and 56.6±0.4kg, p<0.0001; ASMM: 29.4 ±1.3 vs. 24.1±0.4 and 24.3±0.3kg, p=0.0006). Due to limitation in sample sizes, further analysis in subgroups only showed significant associations between TNFa genotype and muscle mass in white males (LM: P<0.0001; ASMM: p=0.0016). CONCLUSIONS: TNFa −308G/A genotype was significantly associated with muscle mass, with AA homozygotes having higher muscle mass than G allele carriers in healthy individuals. Supported by intramural NIH-NIA funds, AG21500 and AG22791.