The Correlation Of KCNQ1 And BCAS3 Gene Polymorphisms With The Susceptibility To Hyperuricemia

Objectives:To investigate the correlation of single nucleotide polymorphisms of KCNQ1 and BCAS3 genes with the susceptibility to hyperuricemia,and their effects on the level of interleukin-1 beta.Methods:The case-control study and the SNaPshot sequencing were used to type gene polymorphisms including rs179785,rs2283228,rs2237892,rs12720449 of KCNQ1 and rs11653176,rs9905274 of BCAS3 in one hundred and twenty hyperuricemia patients as well as one hundred and eighty healthy individuals.The enzyme-linked immunosorbent assay was used to detect the level of serum interleukin-1 beta between the hyperuricemia group and the control group.The baseline data and the levels of interleukin-1 beta between the two groups,and the levels of uric acid and interleukin-1 beta among different genotype subgroups were compared according to the physical examination and biochemical indicators of all subjects.The logistic regression analysis was used to analyze the correlations of the above six loci polymorphisms with the susceptibility to hyperuricemia under different genetic models.The multifactor dimensionality reduction method was also used to analyze whether KCNQ1 and BCAS3 genes interacted with environmental factors in the onset of hyperuricemia.Results:1.The levels of body mass index,systolic blood pressure,diastolic blood pressure,alanine aminotransferase,aspartate aminotransferase,triglyceride,urea,creatinine and uric acid in the hyperuricemia group were higher than those in the control group,while the level of high-density lipoprotein was lower than that in the control group,the above indicators were statistically different between the two groups(P<0.05).No statistically significant differences were found in the levels of glucose,cholesterol and low-density lipoprotein between the two groups(P>0.05).2.There was no statistical difference in the level of interleukin-1 beta between the two groups(P>0.05).3.Either in the hyperuricemia group or the control group,no statistical differences were found in the levels of uric acid and interleukin-1 beta among different genotype subgroups of six loci in KCNQ1 and BCAS3 genes(P>0.05).4.The AC,CC genotypes and C allele of rs2283228 were positively correlated with the risk of hyperuricemia(P<0.05).After adjusting the confounding factors,the risk of hyperuricemia in AC genotype carriers was 5.708 times(95%CI:1.941?16.784)than that in AA genotype carriers under the codominant model.The risk of hyperuricemia in AC or CC genotype carriers was 5.081 times(95%CI:1.176?14.539)than that in AA genotype carriers under the dominant model.Meanwhile,the risk of hyperuricemia in C allele carriers was 2.142 times(95%CI:1.040?4.414)than that in A allele carriers.5.The CT,TT genotypes and T allele of rs2237892 were negatively correlated with the risk of hyperuricemia(P<0.05).After adjusting the confounding factors,the risks of hyperuricemia in CT,TT genotype carriers were 0.193 times(95%CI:0.067?0.559)and 0.077 times(95%CI:0.013?0.444)than that in CC genotype carriers under the codominant model.The risk of hyperuricemia in CT or TT genotype carriers was 0.167 times(95%CI:0.059?0.472)than that in CC genotype carriers under the dominant model.Meanwhile,the risk of hyperuricemia in T allele carriers was 0.260 times(95%CI:0.120?0.561)than that in C allele carriers.6.Whether the confounding factors were adjusted or not,no statistical correlations were found between the genotypes or allele distributions of rs179785,rs12720449,rs11653176,rs9905274 and the risk of hyperuricemia under different genetic models(P>0.05).7.For this study population,the two-factor model composed of rs2237892 and body mass index was the optimal genetic-environmental interaction model in the onset of hyperuricemia.Conclusions:The AC,CC genotype and C allele in rs2283228 of KCNQ1 gene could increase the susceptibility to hyperuricemia,while the CT,TT genotype and T allele in rs2237892 of KCNQ1 gene could reduce the susceptibility to hyperuricemia.The polymorphisms of rs179785,rs12720449 in KCNQ1 gene and rs11653176,rs9905274 in BCAS3 gene would not correlate with the susceptibility to hyperuricemia.For this study population,there was a certain interaction among rs2237892 of KCNQ1 gene,body mass index and age in the onset of hyperuricemia,while no interaction was found between BCAS3 gene and environmental factors.The present study did not find that interleukin-1 beta could affect the onset of hyperuricemia and the above six loci polymorphisms could affect the level of interleukin-1 beta.