Study On HURAT1 Gene Polymorphism And Susceptibility To Hyperuricemia Caused By Pyrazinamide In Yunnan

Objective:To explore the relationship between the rs505802,rs3825016 and rs3825017 single nucleotide polymorphisms(single nucleotide polymorphism,SNP)of human urate transport protein 1(human urate transporter 1)gene and the susceptibility of pulmonary tuberculosis patients to hyperuricemia caused by pyrazinamide in Yunnan Han population,in order to provide effective treatment and take effective preventive measures to minimize or avoid the occurrence of adverse reactions.Methods:294 pulmonary tuberculosis patients with hyperuricemia caused by pyrazinamide and 220 pulmonary tuberculosis patients without hyperuricemia were selected from the Tuberculosis Department of the third people’s Hospital of Kunming from January 2019 to October 2021.Biochemical indexes of all subjects were determined by case-control study,and whole blood DNA extraction,SNP Sequenom Mass ARRAY typing and SNP genotype analysis were performed.The data were analyzed by SPSS 21.0 statistical software.The measurement data were in accordance with normal distribution by t-test and counting data by X~2 test.Logistic regression was used to analyze the rs505802,rs3825016 and rs3825017 polymorphism of h URATl gene and the susceptibility of pulmonary tuberculosis patients to hyperuricemia caused by pyrazinamide.Results:There was no significant difference in sex and age between PIHU(pyrazinamide-induced hyperuricemia)group and control group before and after treatment(X~2=0.042,t=0.065,P>0.05),but there was significant difference in serum uric acid between the two groups(P<0.05).Three genotypes were detected at rs505802,rs3825016 and rs3825017 loci of h URATl gene,which were CC homozygous wild type,CT heterozygous mutant and TT homozygous mutant respectively.The distribution frequencies of rs505802,rs3825016 and rs3825017genotypes in PIHU group were significantly different from those in control group(P<0.05),The frequency of C allele in PIHU group was significantly higher than that in control group,P values were<0.001(X~2=13.489),0.001(X~2=11.479)and 0.007(X~2=7.287),respectively.Pulmonary tuberculosis pati-ents with CC genotype(OR=2.608,95%CI:1.423～4.778,P=0.001)and CT genotype(R=2.376,95%CI:1.278～4.417,P=0.005)at rs3825017 locus have an increased risk of developing PIHU.Pulmonary tuberculosis patients with C allele at rs505802,rs3825016 and rs3825017 loci have an increased risk of hyperuricemia induced by pyrazinamide(OR=1.707,95%CI:1.281-2.274,P<0.001),(OR=1.650,95%CI:1.233-2.207,P=0.001),(OR=1.447,95%CI:1.106-1.893,P=0.007).Conclusion:The polymorphisms of rs505802,rs3825016 and rs3825017 of h URAT1 gene in Yunnan may be associated with the risk of hyperuricemia caused by pyrazinamide in patients with pulmonary tuberculosis,and allele C of rs505802,rs3825016 and rs3825017 may be the risk factors for hyperuricemia induced by pyrazinamide in patients with pulmonary tuberculosis.Rs3825017 CC genotype and CT genotype may be the risk factors for pyrazinamide-induced hyperuricemia in patients with pulmonary tuberculosis.