Gender-Dependent Association of the GNAS1 T393C Polymorphism with Early Aseptic Loosening after Total Hip Arthroplasty

The G-protein G alpha s is involved in the physiology and pathophysiology of bone. Especially, G alpha s is a key regulator of interleukin-6. which is a potent promoter of aseptic loosening. We hypothesi zed that the common single nucleotide polymorphism GNASI T393C 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 Lis 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 = 0.0181) 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 I I-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 GNASI 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. (c) 2008 Orhthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1562-1568, 2008