Association Research Between Single Nucleotide Polymorphisms Of P2X7R Gene And Gouty Arthritis In Chinese Han Population

Background Gout is an inflammatory disease, and IL-1β is believed to be the main cytokine involved in the pathogenesis of acute gouty arthritis. Previous studies showed that monosodium urate crystals (MSU) can participate in the onset of gout by stimulating IL-1β secretion in a variety of ways, however, uric acid signaling is not enough for explanation of some clinical phenomena, for example, some hyperuricemia patients never have onset of gout attack, indicating that there is another pathogenic signal. Our research group demonstrated that more IL-1β is produced from leukocytes stimulated by combing uric acid and ATP in gout patients than hyperuriceamia patients which never had acute attacks, suggesting that ATP-P2X7R axis is main determinant for acute attack of gout arthritis. Previous studies also showed that the regulative ability of P2X7R on IL-1β secretion is affected by P2X7R polymorphisms, the condition of P2X7R is influenced by polymorphisms. Based on these findings, we will estimate the relationship between P2X7R genotype and the pathogenesis of gout, it may provide new insight into the prevention and tretment for acute gouty arthritis.Objective The purpose of this study is to compare frequencies of P2X7R gene non-synonymous SNPs between gouty patients and hyperuricemia patients in Chinese, determine susceptible genotype of P2X7R gene in gout, and analyze the association between single nucleotide polymorphisms of P2X7R gene and gouty arthritis.Methods 117 gouty patients were collected from the outpatient and inpatient department of rheumatism and immunology in Anhui Provincial Hospital.using hyperuriceamia which serum uric acid level exceed 420umol/L (7mg/dl) in not the same two days as control, including 95 persons, both gout and hyperuriceamia patients are male, peripheral venous blood were collected after filling in the questionnaires, then extract DNA, using TaqMan method to detect P2X7R gene polymorism (rs1653624, rs10160951,rs1718119, rs7958316, rs16950860, rs208294, rs17525809, rs2230912) of two groups. The difference of genotype and allele frequwencies was detected by Chi-square test or Fishers exact test, SPSS 17.0 software was used to perform the statistical analyses, the test level was 0.05.Results (1) For rs1653624, genotype frequencies of AA, AT and TT in gouty patients was 41.2% and 50.9% and 7.9%, while 28.3%,57.3% and 17.4% in hyperuriceamia patients, the differences of the distribution of genotype in both groups has statistical significance; allele A and T frequency respectively reached 66.6% and 33.4% in gouty patients,55.4% and 44.6% in hyperuriceamia patients. Allele A may be the susceptibility gene in gout (OR A vs T=1.60895%CI:1.077～2.400, P=0.02).(2) For rs7958316, genotype frequencies of AA, AG and GG in gouty patients was 22.8% and 57.0% and 20.2%, while 11.7%,53.2% and 35.1% in hyperuriceamia patients, the differences of the distribution of genotype in both groups has statistical significance; allele A and G frequency respectively reached 51.3% and 48.7% in gouty patients,38.3% and 61.7% in hyperuriceamia patients. Allele A may be the susceptibility gene in gout (OR A vs G=1.69895% CI:1.147～2.514, P=0.008).(3) For rs17525809, genotype frequencies of TT, CT and CC in gouty patients was 81.7% and 17.4% and 0.9%, while 57.1%,40.7% and 2.2% in hyperuriceamia patients, the differences of the distribution of genotype in both groups has statistical significance; allele Tand C frequency respectively reached 90.4% and 9.6% in gouty patients,77.5% and 22.5% in hyperuriceamia patients. Allele A may be the susceptibility gene in gout (OR T vs C=2.72895%CI:1.545～4.817, P=0.000).(4) Analyzing risk when carry multiple SNPs susceptible gene phenotype:when carried rs1653624 and rs7958316 susceptible gene phenotype,OR reached to 2.580 (95%CI:1.428-4.662, P=0.001); when carried rs1653624 and rs17525809 susceptible gene phenotype,OR reached to 3.971 (95%CI:2.174～7.254, P<0.001); when carried rs7958316 and rs17525809 susceptible gene phenotype,OR reached to 4.207 (95%CI: 2.316～7.642, P<0.001); when carried rs1653624, rs7958316,rs17525809 susceptible gene phenotype,OR reached to 5.071 (95% CI:2.732～9.413, P<0.001).Conclusions whether gout attack in patients with hyperuricemia is associatied with P2X7R gene single nucleotide polymorphism, rs1653624, rs7958316, rs17525809 may be susceptible variant in gout. Hyperuricemia patients with SNP susceptible genotype will suffer gout more possibly.