title: Functional variants of the P2RX7 gene, aseptic osteolysis, and revision of the total hip arthroplasty: a preliminary study.
abstract: Periprosthetic osteolysis (OL) is a major long-term complication of the total hip arthroplasty (THA), which can result in aseptic loosening and revision surgery. Purinergic receptor P2X, ligand-gated ion channel 7 (P2RX7) is an important regulator of inflammation and bone turnover. We were therefore interested in whether functional variants of the P2RX7 gene may be associated with OL and risk of THA failure. A total of 205 unrelated Czech patients with cementless-type THA were stratified according to the severity of acetabular OL and revision of THA. Four "loss-of-function" P2RX7 single nucleotide polymorphisms (SNPs), namely Glu496Ala, Ile568Asn, Arg307Gln, and null allele (rs35933842), were genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP). No significant association of P2RX7 variants with severity of OL was observed. The carriers of rare variants P2RX7 568Asn, 307Gln and null allele, all causing complete loss of P2RX7 function, tended to be overrepresented among patients with THA revision (9.6%) by comparison with those with unrevised functional prosthesis (2.1%, p = 0.09). Furthermore, the carriage of the P2RX7 307Gln allele was associated with greater cumulative hazard of THA revision (p = 0.02). In this preliminary study, we could nominate but not clearly demonstrate rare P2RX7 loss-of-function variants being associated with THA failure. Investigation in large THA cohorts is therefore warranted.
authors.affiliation: Laboratory of Immunogenomics and Immunoproteomics, Medical Faculty of Palacky University and University Hospital, Olomouc, Czech Republic.
authors.forename: F
authors.initials: F
authors.lastname: Mrazek
authors.forename: J
authors.initials: J
authors.lastname: Gallo
authors.forename: A
authors.initials: A
authors.lastname: Stahelova
authors.forename: M
authors.initials: M
authors.lastname: Petrek
mesh_terms: D000328:Adult; D019644:Arthroplasty, Replacement, Hip; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006622:Hip Prosthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010014:Osteolysis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000209:etiology*; D011475:Prosthesis Failure; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058486:Receptors, Purinergic P2X7; D012086:Reoperation
chemical_list: C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7