RESUMEN
Studies of aseptic loosening showed an influence of calcitonin and α-CGRP, both encoded from the calcitonin/α-CGRP (CALCA) gene by alternative splicing. The aim of this study was to detect a possible association of the CALCA polymorphisms P1(rs1553005), P2(rs35815751), P3(rs5240), and P4(rs2956) with the time to aseptic loosening after THA. 320 patients suffering from aseptic loosening after primary total hip arthroplasty were genotyped for CALCA-P1 polymorphism and 161 patients for CALCA-P2 and CALCA-P3 polymorphisms and 160 patients for CALCA-P4 polymorphism. CALCA genotypes were determined by polymerase chain reaction and restriction-fragment length polymorphism. The genotype distribution of CALCA-P1 was CC 10%, CT 43%, and 46% TT. CALCA-P2 showed a distribution of 90.7%II, 8.7% ID, and 0.6% DD. The CALCA-P3 genotype distribution was 97.5% TT and 2.5% TC. The CALCA-P4 genotype distribution was 48.1% AA, 40% AT, and 11.9% TT. Significant differences between the CALCA genotypes were not found concerning age at implantation and replantation, BMI, gender, and cementation technique. No associations of the time for aseptic loosening were found. In conclusion, we did not find a significant association of CALCA polymorphisms and the time to aseptic loosening after primary THA in a Western European group.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Péptido Relacionado con Gen de Calcitonina/genética , Predisposición Genética a la Enfermedad , Falla de Prótesis , Anciano , Femenino , Genotipo , Prótesis de Cadera , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Aseptic 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. METHODS: 231 patients with primary THA and 234 patients suffering from aseptic loosening were genotyped for dependency on GNAS1 genotypes and analyzed. RESULTS: Genotyping 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). CONCLUSION: This 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.
Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Cromograninas/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Polimorfismo de Nucleótido Simple , Complicaciones Posoperatorias/genética , Falla de Prótesis , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación MissenseRESUMEN
Aseptic loosening is a major cause of revision surgery of total hip arthroplasty (THA). Only few host factors affecting aseptic loosening have been identified until now, although they are urgently needed to identify and possibly treat those patients at higher risk for aseptic loosening. To determine whether the functional single nucleotide polymorphism (SNP) c.-938C>A (rs2279115), located in the promoter region of the BCL2 gene has an impact on aseptic loosening of THA we genotyped and analyzed 234 patients suffering from aseptic loosening and 231 patients after primary THA. The polymorphism is associated with risk for aseptic loosening with the CC genotype at highest risk for aseptic loosening, Odds Ratio CC vs. AA 1.93, 95%CI 1.15-3.25, p = 0.013. In contrast, low risk AA genotype carriers that still developed aseptic loosening showed a significantly shorter time to aseptic loosening than patients carrying the C allele (p = 0.004). These results indicate that the BCL2 -938C>A polymorphism influences the occurrence and course of aseptic loosening and suggests this polymorphism as an interesting candidate for prospective studies and analyses in THA registers.