This study assesses interactions of tumor necrosis factor α (TNF-α) gene polymorphisms with C-reactive protein (CRP) or lymphotoxin α (LTA) gene on serum CRP and TNF-α levels and handgrip strength. Eleven single nucleotide polymorphisms (SNPs), including rs2794520, rs1205, rs1130864, rs1800947, and rs3093059 in CRP; rs1799964, rs1800629, and rs3093662 in TNF-α; and rs2239704, rs909253, and rs1041981 in LTA, were genotyped in 472 unrelated elders (mean age 73.8 years). Among elders with TNF-α rs1799964 AA genotype, adjusted mean difference for handgrip strength decreased by -2.60 (-4.82, -0.38) and -2.51 kg (-4.75, -0.28) for LTA rs909253 and rs1041981 in women and by -2.39 kg (-3.98, -0.81) for CRP rs3093059 in men. Among elders with TNF-α rs1799964 AA genotype, adjusted mean ratios for hs-CRP levels increased by 2.32 (1.38, 3.90) and 2.27 (1.35, 3.84) for both CRP rs909253 and rs1041981 in women. The A-A-C LTA haplotype was associated with TNF-α levels that were 1.55 times higher than those of the C-G-A haplotype (P = 0.005). The joint effects of SNPs (the rs1800947 or rs3093059 of CRP, rs1799964 or rs1800629 of TNF-α, and rs909253 or rs1041981 of LTA) and physical inactivity appeared to have greater magnitude of decreased handgrip strength than main effects of these SNPs and physical inactivity. Our data showed that significant interactions of TNF-αrs1799964 and LTA rs909253 were observed. Moreover, joint effects of these CRP, TNF-α, and LTA risk alleles with physical inactivity in elders were observed, suggesting that physical activity may modulate effects of genotypes on handgrip strength.
Keywords: CRP; Handgrip strength; Interaction; Joint effect; LTA; SNP; TNF-α.