尿酸转运相关基因SLC16A9多态性与维吾尔族高尿酸血症关系研究

A study of correlation between uric acid transporter gene SLC16A9 polymorphism and hyperuricemia in Uyghur

目的 尿酸盐的转运和排泄在高尿酸血症的发病中起着关键作用，本研究探讨尿酸转运相关基因SLC16A9的多态性与高尿酸血症的相关性。 方法 采用病例-对照研究的方法，在住院患者中收集高尿酸血症患者1 026例，体检中心筛选对照1 031例，采用Sequenom MassARRAY？ SNP技术检测高尿酸血症组及对照组的尿酸排泄相关基因SLC16A9的4个SNP位点，分析维吾尔族基因变异及与高尿酸血症的关联。 结果 维吾尔族男性血尿酸与体重指数、腰围、空腹血糖呈正相关（r＝0.140，0.237，0.084,均P〈0.01），而与高密度脂蛋白胆固醇（high density lipoprotein-cholesterol, HDL-C）呈负相关（r＝-0.315, P〈0.01）；女性的尿酸与腰围、收缩压、空腹血糖、三酰甘油呈正相关（r＝0.220，0.107，0.165，0.138,均P〈0.05），而与HDL-C呈负相关（r＝-0.468, P〈0.01）。对高尿酸血症进行多因素logistic回归分析，结果显示收缩压、舒张压、三酰甘油、肌酐、低密度脂蛋白胆固醇为高尿酸血症的危险因素，其OR值分别为1.031（95%CI 1.101～1.053）、1.963（95%CI 1.936～1.991）、1.305（95%CI 1.073～1.587）、1.017（95%CI 1.004～1.030）、1.780（95%CI 1.142～2.776）；而HDL-C为高尿酸血症的保护因素，其OR值为0.136（95%CI 0.061～0.303，P〈0.05）。对SLC16A9基因rs1171614位点，在高尿酸组和对照组间是等位基因A相对于G具有保护作用，AA相对于GG差异没有统计学意义（P〉0.05），而AG相对于GG危险性增高且差异有统计学意义（OR＝1.991，95%CI 1.032～3.842, P〈0.01），表明AG杂合子的高尿酸风险高；对rs4948351位点的分析显示TT和CT基因型具有更高的高尿酸血症发病风险（OR＝1.453，95%CI 1.079～1.957；OR＝1.353，95%CI 1.007～1.818），其基因型频率在高尿酸血症组与对照组间差异有统计学意义（P＝0.034），提示rs1171614和rs4948351与高尿酸血症的发生有关联。 结论 研究显示SLC16A9基因与与维吾尔族高尿酸血症的发病机制有较密切的关系。

Objective The transport and excretion of uric acid play significant role in occurrence of hyperuricemia. The correlation between polymorphism of the gene （SLC16A9） and the occurrence of hyperuricemia was explored in this study. Methods Case-control study was used in this research in which 1 026 patients with hypeturicemia were collected in the hospital, while 1 031 control cases were selected from regular medical check- ups. Sequenom MassARRAY SNP was utilized in both hyperuricemia and control groups to detect the correlation between 4 SNP sites of SLC16A9 mutation related to uric acid excretion in order to analyze the association between gene mutation and hyperuricemia among Uyghur. Results In males, blood uric acid has a positive association with body mass index, waist circumferences, fasting blood glucose （r = 0. 140,0. 237,0. 084, all P〈0.01 ） ; while a negative relationship with high density lipoprotein-cholesterol （ HDL-C ） was found （r = -0.315, P〈0.01 ）. While in females, there were positive relationships in blood uric acid and waist circumferences, systolic blood pressure, fasting blood glucose, and triglyeeride（ r=0. 220,0. 107,0. 165,0. 138, all P〈0.05 ）, while negative relationship to the HDL-C was found （ r=-0. 468, P〈0.01 ）. Multivariate logistic regression demonstrates that both systolic and diastolic bloodpressures, triglycerides, creatinine, and low density lipoprotein-cholesterol are risk factors of hyperuricemia, and the OR were 1. 031 （95% CI 1. 101-1. 053）, 1. 963 （95% CI 1. 936-1. 991 ）, 1. 305 （95% CI 1. 073-1. 587）, 1. 017 （95% CI 1. 004-1. 030）, and 1. 780 （95% CI 1. 142-2. 776） respectively. However, HDL-C is a protective factor, OR was 0.136 （ 95 % CI 0. 061-0. 303, P〈0.05 ）. The A and G genotype of rs 1171614 of SLC 16A9 seems to have a protective effect in both groups, there is no significant difference between AA and GG（P〉0.05 ）. As compared with GG genotype, AG heterozygote has a high risk （ OR= 1. 991,95% CI 1. 032-3. 842, P〈0.01 ）. More importantly, rs4948351 stie revealed that TI＂ and CT also had a higher risk（ OR= 1. 453,95% CI 1. 079-1. 957 ;OR= 1. 353,95% CI 1. 007-1.818 ） , and there was a significant difference between two groups （P = 0. 034 ）, suggesting that rs1171614 and rs4948351 associated with hyperuricemia. Conclusion The study further confirms the relationship between the SLC16A9 gene and the pathogenesis of hyperuricemia.