Polymorphisms In 3'-Untranslated Region Of Human Urate Transporter 1 Related To Hyperuricemia And Gout

Objective:hURAT1 is the mian gene of regulating surem uric acid,and it is one of the most important candidate genes of primary hyperuricemia.The present case - control study was designed to find SNPS and mutations in 3'-untranslated region of URAT1 related to primary hyperuricemia and gout。Method:We included 273 primary hyperuricemia patients,429 healthy volunteers。DNA was purified from peripheral blood and 3' UTR of the URAT1 gene in patients and control individuals were screened for mutations by polymerase chain reaction(PCR) and subsequent forward and reverse sequencing.SNPs and mutations on hURAT1 were recogonized by Genestar software;To evaluate chooseing samples to fit random principle,all SNPs of subjects were computed by haploview software;genotype and allele frequencies between groups compared byχ~2 test to identificate related polymorphisms on hURAT1 gene with hyperuricemia;Individual haplotypes from related polymorphisms were estimated by the Phase software to discriminate susceptive haplotypes on hURAT1 gene with hyperuricemiaoResult1.hURAT1 gene sequencing result3 single nucleotide polymorphisms were founded in this region:1925 G＞A,del G 1951 and G 2174 A。del G 1951 had been reported in NCBI.1925 G＞A and G 2174 A were new founded SNPs.del TC 1827-1828 was found in only two patients.2.Hardy-Weinberg equilibrium testNo deviations from Hardy-Weinberg equilibrium were observed for 3 polymorphisms of 702 individuals,indicated all samples were chosen randomly.(P=0.473,0.748,0.917)3.Genotype and allele frequencies in cases and controls. Genotype and allele frequencies between groups has no significant diference(P＞0.05).4.hURAT1 haplotypes in 3' UTR.We estimated the hURAT1 haplotypes of 3 SNPs in the cases and controls separately.The 3 SNPs composed with 5 haplotypes,in which 2 haplotypes had a frequency of less than 2%were excluded in the analysis.3 haplotypes covered 98%people were received.According to the result,none of haplotypes was associated with a significantly increased risk of hyperuricemia.5.The del TC 1827-1828.The del TC 1827-1828 was found in two distribute patients,no any of 429 healthy volunteers.The two patients have high serum uric acid(573μmol /L,630μmol/L VS 499.69±136.08μmol/L).But this mutation only happened 0.733%,indicated that it may associated with hyperuricemia,but not a main reason.Conclusion3 SNPs detected in this region can be used as genetic markers.The del TC 1827-1828 mutation was supposed to be a pathogenic site of hyperuricemia,more samples should be screened,and further function studies are needed to confirm whether this delection cause high expression of hURAT1 gene.