Association Between Genetic Polymorphisms Of SLC2A9, ADRB3, GNB3 And Hyperuricemia

Objective: The resent study aimed to investigate the association between rs3775948,rs502843 of the SLC2A9 gene,rs5443 of the GNB3 gene and rs4994 polymorphism of the ADRB3 gene and hyperuricemia.Detecting the serum uric acid-related genes and provide a theoretical,scientific advice for the prevention and treatment of hyperuricemia and other common chronic diseases.Methods: 1.Retrospectively collected data from a physical examination institution in Yinchuan.Using 1:1 matching case-control study and according to certain inclusion criteria,367 subjects were selected as case group.367 normal subjects were selected as a control group with age(±5),same gender and ethnicity as the matching conditions.2.The research included four parts: questionnaire,physical examination,laboratory biochemical indicators and genotyping test.The general demographic characteristics of the subjects were investigated.The physical examination included the measurement of height and weight,calculated the body mass index(BMI=weight/height2),measured the blood pressure.The biochemical indexes included serum uric acid,creatinine,triglycerides,total cholesterol,high density lipoprotein,low density lipoprotein and fasting blood glucose;blood samples were collected for genotyping test.3.Statistical analysis: The paired t test was used to analyze the differences of the physical examination indexes between the case group and the control group.Paired c2 tests was used to analyze the distribution of SLC2A9 rs3775948,rs502843,GNB3 rs5443 and ADRB3 rs4994 genotypes between case and control groups;Conditional logistic regression analysis was used to analyze the influencing factors of hyperuricemia;The influence of interaction between rs3775948 and rs502843 of SLC2A9,rs5443 of GNB3 and rs4994 of ADRB3 on hyperuricemia was analyzed by multivariate dimensionality reduction(MDR).All the analysis was performed with SPSS software.Results: 1.The genetic response rates of rs3775948 and rs5443 were 99.6%,and the response rates of rs502843 and rs4994 were 100%,99.9%,respectively.2.A total of 360 pairs were selected in this study after excluded those non-genetic response.There were 229 males(63.6%)in each group,168(46.7%)Han and 192 Hui(53.3%).The age of case group was range from 29 to 80 years old,with an average age of(56.58±9.24).The control group was from 29 to 81 years old with an average age of(56.57±9.34).3.The comparison of physical examination indexes between two groups: The Creatinine,SUA,SBP,TC,TG and BMI between two groups had significantly statistical difference(P<0.05).The means of all the indexes in case group were higher than that in control group.The levels of blood glucose(FPG),diastolic blood pressure(DBP),blood urea nitrogen(BUN),high density lipoprotein(HDL),low density lipoprotein(LDL)in the two groups had no significant difference(P>0.05).4.The distribution of genotypes between case group and control group: The distribution of rs3775948 genotype of SLC2A9 gene was statistically significant between case group and control group,in which G was wild allele and C allele was effect alleles.The frequency distribution of wild homozygote G/G genotypes in the control group was higher than that in the case group(41.1% vs.32.2%).The frequencies of the mutant homozygote C/C genotypes in the case group was higher than that in the control group(18.3% vs.9.5%).There was no significant difference of rs502843,rs5443 and rs4994 between two groups.5.Multivariate analysis: Conditional logistic regression was used to analyze the influencing factors of hyperuricemia.The creatinine,systolic blood pressure,diastolic blood pressure,triglycerides,body mass index were the influencing factors,which were positively correlated with hyperuricemia,each of them increased by one unit,the risk of the disease increased by 1.034,1.027,1.569 and 1.114 times in turn;Diastolic pressure was negatively correlated with the incidence of the disease;SLC2A9 gene rs3775948 locus associated with the occurrence of hyperuricemia,Compared to G/G genotype,the risk of C/C genotype is 2.229 times than G/G genotype(OR=2.229).6.Genetic model analysis: The rs3775948 locus of SLC2A9 conformed to the dominant and recessive genetic models in the overall subjects.The risk of G/C+C/C genotype to hyperuricemia was 1.468 times than G/G genotype,and the risk of C/C genotype was 2.152 times than it.The rs502843 locus of SLC2A9 conformed to the dominant models.rs5443 of GNB3 gene and rs4994 of ADRB3 gene didn't conformed to anyone models.7.Interaction analysis: There was a strong antagonism between SLC2A9 gene rs3775948 and rs502843,and there was no interaction between the other locus.Conclusion: 1.rs3775948 locus of SLC2A9 gene and rs502843 locus were associated with the occurrence of hyperuricemia in this physical examination population.2.The influencing factors of hyperuricemia in this physical examination population were Creatinine,blood pressure,triglycerides and body mass index.3.There was a strong antagonism between SLC2A9 gene rs3775948 and rs502843.