Gender-dependent association of the GNAS1 T393C polymorphism with early aseptic loosening after total hip arthroplasty.

The G-protein Galphas is involved in the physiology and pathophysiology of bone. Especially, Galphas is a key regulator of interleukin-6, which is a potent promoter of aseptic loosening. We hypothesized that the common single nucleotide polymorphism GNAS1 T393C could also affect time to aseptic loosening. Caucasian patients were genotyped for the GNAS1 T393C polymorphism. Time and median time to aseptic loosening were analyzed for dependency on GNAS1 genotypes. Time and median time were not significantly associated with genotypes. Additional analysis corrected for gender revealed, that the TT genotype was associated with significantly longer time (p = 0.048) as well as median time (p = 0.022) to aseptic loosening in female patients. In contrast to the findings in females, male TT genotype carriers had significantly shorter time (p = 0.018) and median time (p = 0.023) to aseptic loosening. Compared with TT genotype carriers heterozygous patients had a 6.25-fold lower risk with a hazard ratio of 0.160 (p = 0.016) and male patients carrying the CC genotype had an 11-fold lower risk with a hazard ratio of 0.088 (p = 0.006) in multivariate analysis. The present study suggests a significant gender-dependent role of the T393C polymorphism in aseptic loosening. The apparently contradictory results in women and men and the finding that the GNAS1 T393C genotype is an independent factor for time to aseptic loosening in male patients assigned this polymorphism as an interesting target for further investigations in bone diseases.