| Objective: To investigate the single nucleotide polymorphisms(SNPs)(rs10489070,rs734553,rs3733591,rs16890979) of SLC2A9 gene in ChineseHan population, and to explore the association of this gene polymorphismswith gout susceptibility, tophi, serum uric acid levels, other clinical andlaboratory data and the levels of SLC2A9 mRNA on peripheral bloodmononuclear cells(PBMCs) .Methods: 1.A total of 297 primary gout arthritis patients(GA) and 211healthy controls(HC) were enrolled into this study. The clinical and laboratorydata of samples such as serum uric acid(UA), fasting blood glucose(FBG),serum total cholesterol(TC), serum total triglycercide (TG),high densitylipoprotein cholesterol (HDL-C) were collected.2.The blood samples weretaken and the genomic DNA were extracted from peripheral blood .Thegenotypes and alleles frequencies were calculated by using TaqMan SNPGenotyping Assays and the possible association between gene polymorphismsof SLC2A9 and gout was investigated by using Chi-square test . The oddsratios (OR) and 95% confidence intervals (95% CI) were calculated .Student’s t-test or analysis of variance was used to assess a significantdifference in demographic and clinical characteristics among differentgenotype carriers. 3.Isolate PBMCs of sub-group 120 samples from goutpatients and controls to extract total RNA,then to be reverse transcribed intocDNA .The levels of SLC2A9 mRNA on PBMCs were measured by usingreal-time quantitative polymerase chain reaction (RT-qPCR).The nonparametric test was used to analysis the expression of different groups.Results:1.Gout patients were matched for age and gender to controlindividuals.The BMI,systolic blood pressure(SBP),diastolic bloodpressure (DBP) and the levels of serum uric acid(UA), fasting bloodglucose(FBG),serum total cholesterol(TC),serum triglycercide (TG),Creatinine(CR),Urea nitrogen(BUN) were much higher in goutcases,while the levels of high density lipoprotein cholesterol (HDL-C)was much lower than controls(P<0.05).2.All 4 SNPs followedHardy-Weinberg equilibrium in controls (P>0.05). The frequencies of CC,TCand TT genotypes of rs3733591 in gout patients were 15.8%,46.5%,37.7%respectively, while the frequencies of CC,TC and TT genotypes of rs3733591in controls were 10%,41.7%,48.3% respectively. There was significantlystatistical difference in genotype frequencies between two groups(P<0.05).The allele frequencies of T and C in gout cases were also different fromcontrol subjects (60.9%,39.1% vs 69.2%,30.8%,P<0.05). There was nostatistical differerce in distribution frequencies of genotypes and alleles ofothers between two groups(P>0.05).3.The distribution frequency ofrs3733591 CC genotype combined with rs10489070 CC genotype in caseswas much higher than in controls(P<0.05).And there was significantlystatistical difference in distribution frequencies of all wild type homozygousgenotype combinations between two groups(14.8% vs 8.1%,χ~2=5.332, P<0.05)and the relative risk of this genotype combinations to develop to gout was1.985 (95%CI: 1.100-3.581).4.There was no significantly statistical differencein genotype frequencies and alleles between tophi patients(30) and non-tophipatients(190). 5.Logistic regression analysis showed that the gender,UA,FBG,TG,LDL-C were the correlation fators of gout. 6.The levels of serum urate acid of individuals carried CC genotype of rs10489070 were muchhigher than those carried CG genotype (P<0.05),while the levels ofapolipoprotein A1(apoA1) were much lower (P<0.05).7.The expression ofSLC2A9 mRNA on PBMCs in gout patients was remarkably lower comparedwith healthy controls(P<0.05), and the expression of SLC2A9 mRNA onPBMCs in acute gouty arthritis patients was much higher than in intervalgouty arthritis patients(P<0.01). Moreover,the levels of SLC2A9 mRNA ingout patients who carried TG genotype of rs3733591 was higher than thosewho carried TT genotype(P<0.05).There was no difference of the expressionof SLC2A9 mRNA on PBMCs among different genotype carriers ofrs3733591 and others in controls(P>0.05). Furthermore, spearman correlationanalysis found that the expression of SLC2A9 mRNA had significantlycorrelation with the numbers of lymphocyte in peripheral blood(r_s=-0.295,P=0.015), but not with serum uric acid levels(P>0.05).Conclusions:1.The single nucleotide polymorphism of SLC2A9(rs3733591) possibly has association with gout in Chinese Han populationand the levels of SLC2A9 mRNA on PBMCs of gout.The C allele ofrs3733591 may be a genetic maker of gout.2.The single nucleotidepolymorphism of SLC2A9 (rs10489070) probably has relation to the levels ofserum urate acid and apoA1 of Chinese Han people.3.Gender,UA,FBG,TGand LDL-C may be the risk fators of gout.4.The present data shows thepolymorphisms of SLC2A9 gene (rs10489070, rs734553, rs3733591,rs16890979) have no association with tophi gout patients. 5.The expressingof SLC2A9 mRNA on PBMCs in gout paitents is abnormal,which may alsobe involved in gouty arthritis attack. |
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