中国男性痛风患者SLC2A9基因单核苷酸多态性与尿酸水平的关系

Molecular analysis of a SNP in SCL2A9 and uric acid levels in Chinese male gout patients

目的SLC2A9是新近发现的尿酸转运子，该基因单核苷酸多态性可影响血清尿酸水平。本研究检测SLC2A9基因第6内含子rs7442295多态性在中国男性痛风和原发性高尿酸血症患者中的分布情况以及与尿酸代谢指标的相关性。方法选取268例原发性痛风患者和288名健康志愿者，分别检测血压、体质量指数、血尿酸、血糖、血脂、肾功能水平，并同时提取外周血DNA，运用高分辨率熔解曲线（HRM）分析rs7442295基因型，并用测序法证实。统计学方法采用矿检验及t检验。结果运用HRM技术能准确区分rs7442295～A和A／G基因型，而G／G基因型则在本研究人群中未发现。A／A和A／G基因型在人群分布频率分别是96．2％和3．8％。与健康对照组相比，痛风组的A／A和A／G基因型频率及A、G等位基因频率分布差异无统计学意义（矿=0．003，P=0．82；x2=0．003，P=1．00），但携带A／G基因型个体的尿酸水平[（293±100）μmol／L]明显低于携带A／A基因型的个体[（392±133）μmol／L]（t=2．426，P〈0．01），且正常尿酸组内A／G基因型频率明显高于高尿酸组0（2=6．279，P=0．01），基于HRM技术的基因分型结果与测序法所得结果完全一致。结论SLC2A9基因~7442295多态性可能是评估中国汉族男性人群原发性高尿酸血症危险性的一个遗传学标志，HRM技术简单、方便、快速，并实现闭管检测，非常适合单核苷酸多态性分析。

Objective SLC2A9 is a novel identified urate transporter that affects serum uric acid levels. The present study is aimed to investigate rs7442295 polymorphism in intron 6 of SLC2A9 in a popula- tion of Chinese male gout or hyperuricaemia subjects. Methods A total of 268 gout patients and 288 healthy male volunteers were included. Blood pressure, body mass index （BMI）, serum uric acid, glucose, lipid, urea and creatine were detected. DNA was purified from peripheral blood and the rs7442295 polymorphism was evaluated using high resolution melting （HRM） analysis and direct sequencing. Data wele analyzed with t test or chi-square test. Results A/A and A/G genotypes were unambiguously distinguished with HRM technology. The occurrence of the homozygous type （G/G） was completely absent among the study population. The prevalence of the A/A and A/G genotype was 96.2% and 3.8% respectively. However, no significant differences of genotype frequencies were found in gout patients and normal subjects （X2=0.003, P=0.82; X2= 0.003, P=1.00）. But the serum uric acid levels in individuals with the A/G genotype [（293±100） μmol/L] were significantly lower than those with the A/A genotype [ （392±133） μmol/L] （t=2.426, P〈0.01 ）. The A/G genotype frequency was significantly higher in the low-urlc acid group than in the high uric-acid group 6.279, P=0.01）. Genotyping based on HRM was fully concordant with sequencing. Conclusion x2= The polymorphism rs7442295 in SLC2A9 may be a genetic marker to assess risk of hyperuricemia among Chinese male Han population. HRM is a simple, fast, reliable and close-tube technology for genotyping.