THU0532 Genetic Analysis for P2x7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Male Korean Population

Abstract

BackgroundThe NLRP3 inflammasome, a member of the NLR family, is a key player in the production of uric acid-mediated IL-1β and is an important cytoplasmic protein complex involved in gouty inflammation. Recent single-nucleotide polymorphism (SNP) studies suggested that genetic alternations of several target molecules such as CARD8 and P2X7R contribute to the process of NLRP3 inflammasome activation.ObjectivesThe aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects.MethodsThis study enrolled a total 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142 (C>A) in the P2X7R gene and rs2043211 (A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses.ResultsA difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (p>0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed a protective effect of P2X7R/CARD8 AA/AA against gout susceptibility (OR=0.023, 95% CI 0.874–0.999).ConclusionsThis study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.ReferencesMartinon F, Pétrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006;440:237–41.Choe JY, Jung HY, Park KY, et al. Enhanced p62 expression through impaired proteasomal degradation is involved in caspase-1 activation in monosodium urate crystal-induced interleukin-1b expression. Rheumatology (Oxford) 2014;53:1043–53.Yang SK, Kim H, Hong M, et al. Association of CARD8 with inflammatory bowel disease in Koreans. J Hum Genet 2011;56:217–23.Chen Y, Ren X, Li C, et al. CARD8 rs2043211 polymorphism is associated with gout in a Chinese male population. Cell Physiol Biochem 2015;35:1394–400.Gu BJ, Zhang W, Worthington RA, et al. A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor. J Biol Chem 2001;276:11135–42.Disclosure of InterestNone declared