The BCL2 -938C>A Promoter Polymorphism Is Associated with Risk for and Time to Aseptic Loosening of Total Hip Arthroplasty

Abstract

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.

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

“…The advantages of a genetic host factor as a prognostic marker would be an easy determination, realizable prior to surgery. In recent years, some promising polymorphism in different genes such as the Matrix metalloprotease 1 [ 33 ], the Tissue Inhibitor of Metalloproteinase 1 [ 34 ], or BCL2 [ 27 ] were identified and their impact on risk for and time to aseptic loosening were investigated. Despite significant associations of these polymorphisms with risk for and time to aseptic loosening, up to date, none of these polymorphisms is determined routinely.…”

“…Our retrospective case–control study included 465 Western European patients of German ancestry operated at the Helios ENDO-Klinik Hamburg, Germany [ 27 ]. The control group consisted of 231 patients with primary THA without aseptic loosening and the case group consisted of 234 patients suffering from aseptic loosening after THA.…”

“…To date, no further analyses have been performed to validate these findings in independent studies. Therefore, we used a recently established independent cohort comprising 234 patients suffering from aseptic loosening and 231 patients with primary THA to prove the putative association of the GNAS1 T393C polymorphism with aseptic loosening [ 27 ].…”

Polymorphisms of BCL2 Gene in Acute Lymphoblastic Leukemia Patients in Pakistan and Screening of Phytochemicals to Overcome its Expression

“…It consists of 6 exons which encodes for 239 amino acid protein having weight 26266 Da. It comprises of two functional domains BH4 (amino acid [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and a hydrophobic cleft formed of BH3 (amino acid 90-107), BH2 (amino acid 184-199), and BH1 (amino acid 133-152). A helical transmembrane domain (amino acid 212-233) is also present which is required for membrane anchoring.…”

“…A study on SNP 938 C/A showed that presence of C allele has a significant effect on promoter 2 activation; the increase in interaction between the promoter and transcription factors lowers the BCL2 protein level [12]. This SNP is present as 5 prime UTR variant located near promoter region [13].…”