| Objective Association study on relationship between genetic polymorphisms of SLC22A12 rs893006 and rs7929627 and SLC2A9 rs10489070 with hyperuricemia in Ningxia Hui Autonomous Region. Subjects come from a check-up institution, including Hui and Han individuals. In order to provide a theoretical basis for different ethnicity population genetic studies of hyperuricemia, lay a foundation for an efficient and scientific prevention and treatment of hyperuricemia.Methods 1. The cases, according to the inclusion and exclusion criteria, were diagnosed in a certain medical institution without relationship individuals 361 as the case group. The number of men was 227, women was 134, Han ethnicity was 167, Hui ethnicity was 194. The age range were from 29 to 80 years old, mean age were 56.75± 9.32 years old.At the same time, the healthy individuals, according to gender, ethnicity and age(no more than 5 years), were checked in the same medical institution with similar background,matched with 1:1 for case group as the control group. The age range were from 28 to 79 years old, mean age were 56.67± 9.26 years old for the control group.2. The subjects of demographic questionnaire, physical examination and laboratory biochemical tests results were collected. Sequenom Mass ARRAY i PLEX GOLD technology was performed to analyze the SNPs site genotype of the case and control groups for SLC22A12 gene rs893006, rs7929627 and SLC2A9 gene rs10489070 with peripheral blood specimens. The Hardy-Weinberg equilibrium law test was used to analyze whether the gene frequency of control group represented the distribution of population genetic. Chi-square test was used to analyze the distribution of genotypes and allele frequencies for the different groups, T-test was performed to analyze the quantitative data, Analysis of Variance was performed to compare the difference for multiple groups of quantitative data.MDR software was used to analyze the gene interaction of SLC22A12 gene rs893006,rs7929627 and SLC2A9 gene rs10489070 SNPs site. Logistic regression was used to analyze the influential factors of hyperuricemia.Results 1. Comparison of biochemical indicators There were significantly different between case and control group of Crea, TC, TG, SBP and BMI mean value, the case group were higher than control. There were not significantly different between case and control group of mean difference for BUN, FBG, HDL, LDL and DBP.2. Genotype distribution In the case group, SLC22A12 gene rs893006 site GG genotype frequency was 184, GT genotype frequency 145, TT genotype frequency 32,SLC22A12 gene rs7929627 site AA genotype frequency was 139, AG genotype frequency158, GG genotype frequency 64. SLC2A9 gene rs10489070 site CC genotype frequency was284, CG genotype frequency 74, GG genotype frequency 3. In the control group SLC22A12 gene rs893006 site GG genotype frequency was 194, GT genotype frequency 148, TT genotype frequency 19, SLC22A12 gene rs7929627 site AA genotype frequency was 107,AG genotype frequency 193, GG genotype frequency 61. SLC2A9 gene rs10489070 site CC genotype frequency was 287, CG genotype frequency 67, GG genotype frequency 7.3. Genotype analysis There were significant difference between case and control group of SLC22A12 gene rs7929627 site genotype frequency(c2 = 7.725, p = 0.021),there were not significantly different between case and control group of SLC22A12 gene rs893006 site and SLC2A9 gene rs10489070 site genotype and allele frequency. With the help of different genetic model, we discovered that SLC22A12 rs7929627 site implicit model genotype frequency was statistically significant difference(c2= 6.314, p = 0.012), carrying AA genotype person have 1.49 times risk for incidence of hyperuricemia than carrying AG+GG genotype. There was not statistically significant difference between case and control group of SLC2A9 gene rs10489070 site and SLC22A12 gene rs893006 site with different genetic models.4. Stratification analysis There were not statistically significant difference between different ethnicity and different gender with different genotypes and allele frequency in case and control group, including SLC22A12 gene rs893006, rs7929627 SNPs site and SLC2A9 gene rs10489070 SNP site. There were not statistically significant difference between case and control group with different genotypes and allele frequency in Han group, including SLC22A12 gene rs893006, rs7929627 SNPs site and SLC2A9 gene rs10489070 SNP site. There were not statistically significant difference between case and control group with different genotypes and allele frequency in Hui group, including SLC22A12 gene rs893006 and SLC2A9 gene rs10489070 SNPs site. There were significant difference between case and control groups of SLC22A12 rs7929627 site genotype frequency in Hui group(c2 = 6.844, p = 0.033), while there were not significant difference in allele frequency, carrying AA genotype individuals have 1.67 times risk for incidence of hyperuricemia than carrying AG+GG genotype. There were significant difference between case group and control group of SLC22A12 gene rs893006, rs7929627 SNPs site genotype frequency in male individuals(c2 = 6.384, p = 0.041; c2 = 7.378, p = 0.025), while there were not significant difference in allele frequency. There were not significant difference between case group and control group of SLC2A9 gene rs10489070 SNP site genotype and allele frequency in male individuals. With the help of different genetic model, in male group carrying GT and GG genotype of SLC22A12 gene rs893006 SNP site has 0.41 times risk for incidence of hyperuricemia than carrying TT genotype, carrying AA genotype of SLC22A12 gene rs7929627 SNP site has 1.67 times risk than carrying AG+GG genotype for incidence of hyperuricemia. There were not statistically significant difference between case and control group of SLC22A12 gene rs893006, rs7929627 SNPs site and SLC2A9 gene rs10489070 SNP site genotype and allele frequencies in female.5. Mean value compared among different genotypes for biochemical indices There were not significant difference among SLC22A12 gene rs893006 and rs7929627 and SLC2A9 gene rs10489070 SNPs site genotypes frequency with different biochemical indicators, such as BUN, Crea, FBG, TC, TG, LDL, HDL, SBP, DBP, or BMI.6. Logistic regression analysis Logistic regression analysis showed that Crea,TG and BMI were risk factors for hyperuricemia(P<0.05).7. Gene interaction analysis Gene interaction analysis showed that carrying GG genotype of rs893006 and carrying CC genotype of rs10489070 and carrying AA and AG genotype of rs7929627, and carrying GT genotype of rs893006 and carrying AA genotype of rs7929627 and carrying CC and CG genotype of rs10489070,and GT genotype of rs893006 and carrying AG genotype of rs7929627 and CG genotype of rs10489070, and carrying TT genotype of rs893006 and AA genotype of rs7929627 and CC, CG, GG genotype of rs10489070, which were high risk genotype individuals of hyperuricemia. There was significant difference for the composition of high-risk genotype between case and control group, carrying high-risk genotype individuals have 1.83 times risk for incidence of hyperuricemia than low-risk genotype. There was not significant difference between Hui and Han ethnicity group of the composition for the high-risk genotype. Maybe, SLC22A12 gene and SLC2A9 gene have a weak synergy effect, while SLC22A12 gene rs7929627 and rs893006 SNPs site have an obvious antagonistic effect.Conclusions 1. SLC22A12 gene rs7929627 SNP site genotype is associated with the incidence of hyperuricemia, and SLC22A12 gene rs7929627 SNP site genotype is associated with the incidence of hyperuricemia in Hui ethnicity group.2. SLC22A12 gene rs893006 and rs7929627 SNPs site are associated with the incidence of hyperuricemia in male group.3. There are risk factors of hyperuricemia, such as Crea, TG and BMI.4. Carrying high-risk genotypes have 1.83 times risk for incidence of hyperuricemia than carrying low-risk genotype. SLC22A12 gene and SLC2A9 gene have a weak synergy effect, while SLC22A12 gene rs7929627 and rs893006 have an obvious antagonistic effect. |
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