Relationship between GNAS1 T393C polymorphism and aseptic loosening after total hip arthroplasty

Abstract

BackgroundAseptic loosening is a main cause for revision surgery after total hip arthroplasty (THA) and there is no reliable marker for the early detection of patients at high risk. This study has been performed to validate association of the T393C polymorphism (rs7121) in the GNAS1 gene, encoding for the alpha-subunit of heterotrimeric G-protein Gs, with risk for and time to aseptic loosening after THA, which has been demonstrated in our previous study.Methods231 patients with primary THA and 234 patients suffering from aseptic loosening were genotyped for dependency on GNAS1 genotypes and analyzed.ResultsGenotyping revealed almost similar minor allele frequencies of 0.49 and 0.46, respectively. Consistently, genotype distributions of both groups were not significantly different (p = 0.572). Neither gender nor GNAS1 genotype showed a statistically significant association with time to loosening (p = 0.501 and p = 0.840). Stratification by gender, as performed in our previous study, was not able to show a significant genotype-dependent difference in time (female p = 0.313; male p = 0.584) as well as median time to aseptic loosening (female p = 0.353; male p = 0.868).ConclusionThis study was not able to confirm the results of our preliminary study. An association of the GNAS1 T393C polymorphisms with risk for and time to aseptic loosening after THA is unlikely.

The 2018 Otto Aufranc Award: How Does Genome-wide Variation Affect Osteolysis Risk After THA?

“…set low (typically at p < 0.05), favoring the identification of a positive association. Although these discovery studies lend support to the concept of a disease driven by heritable variation, these associations commonly are not reproduced when examined in independent cohorts [46], and the overall contribution of genetic variation to the disease remains unanswered. In contrast, genome-wide studies allow examination of the overall genetic architecture of the disease that underpins the differences in susceptibility between individuals.…”

Development of an Integrated Platform Using Multidisciplinary Real‐World Data to Facilitate Biomarker Discovery for Medical Products

“…GNAS‐rs7121 in particular was initially suggested as a risk factor for aseptic loosening in males . Although the subsequent evidence linking rs7121 to aseptic loosening seems contradictory, GNAS‐rs7121, to our knowledge, remains the only SNP that has been thus far associated with the sex‐related differences in hip replacement outcomes. Because GNAS‐rs7121 and some other SNPs linked to adverse outcomes in hip replacement were included into the panel of disease‐associated SNPs used in the PMRP, we utilized pre‐existing PMRP SNP data ( Table ) to test the putative sex‐dependent role of GNAS‐rs7121 and other available SNPs in the hip replacement‐related adverse outcomes.…”

“…9,[12][13][14][15] GNAS-rs7121 in particular was initially suggested as a risk factor for aseptic loosening in males. 16 Although the subsequent evidence linking rs7121 to aseptic loosening seems contradictory, 17,18 GNAS-rs7121, to our knowledge,…”

No Association of CALCA Polymorphisms and Aseptic Loosening after Primary Total Hip Arthroplasty

“…SNPs of important cytokines in PIO like interleukin-6, tumor necrosis factor- α , and transforming growth factor- β 1 were suggested to predict the time to onset of PIO [ 35 ]. A study of the T393C polymorphism (rs7121) in the GNAS1 gene could not find an association with risk for and time to aseptic loosening after THA [ 36 ]. XIONG et al did not find an association of the calcitonin receptor AluI gene polymorphism and bone mineral density [ 37 ].…”