高尿酸合并高血压患者URAT1 6092(T/C)基因多态性对氯沙坦降尿酸疗效的影响

目的: 探讨尿酸盐阴离子转运体(Urate Transporter 1,URAT1)SNP6092(T/C)基因多态性对高尿酸血症合并原发性高血压患者服用氯沙坦降尿酸疗效的影响。方法: 应用PCR-RFLP方法对101名高尿酸血症合并原发性高血压患者和117名健康对照者进行基因分型,并且所有患者均每天口服氯沙坦药物 100 mg,连服2周。测定用药前后的血压、血尿酸(Ur)、尿素氮(BUN)、肌酐(Cr)、胆固醇(CHOL), 高密度脂蛋白胆固醇(HDL-c), 低密度脂蛋白胆固醇(LDL-c)和甘油三酯(TG)。结果: 服用氯沙坦后,突变基因型患者(TC/CC)的Ur和Cr的降低水平均明显低于TT基因型患者(P<0.05),并且TC和CC型患者的Ur降低幅度(1.34%±2.12%,-0.2%±3.8%)也明显低于TT基因型患者(22.58%±14.46%)(P<0.05)。结论: URAT1基因6092T/C遗传变异影响氯沙坦的降尿酸疗效,并且可能是氯沙坦降尿酸潜在的遗传靶点。

URAT1 allele 6092(T/C) polymorphism influence uricosuric action of losartan in hyperuricemia patients with hypertension

AIM: To investigate the effect of URAT1 6092(T/C) polymorphism on uricosuric action of losartan in Chinese hyperuricemia patients with hypertension.METHODS: A total of 101 patients and 117 healthy controls were enrolled to identify 6092T/C genotypes by polymerase chain reaction restriction fragment length polymorphism assay.All patients received orally losartan as a single-dose therapy (100 mg/d p.o.) for 2 weeks. The blood pressure,serum creatinine(Cr), blood urea nitrogen (BUN),serum uric acid(Ur), total cholesterol(CHOL), high-density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and triglyceride(TG) were determined before and after losartan treatment.RESULTS: After treatment,patients with the T6092C polymorphism TC/CC genotype showed significant lower levels. Compared with patients with the TT genotype,the decreased value and percentage of Ur, Cr was low ,moreover, patients with CT/CC genotype also showed significant lower levels of decreased percentage of Ur (1.34%±2.12%,-0.2%±3.8%) compared with patients with the TT genotype (22.58%±14.46%)(P<0.05).CONCLUSION: These results suggest that URAT1 6092(T/C) polymorphism can influence the uricosuric action of losartan and it is potential genetic markers for the optimization of losartan uricosuric action.