高尿酸血症TNF-a启动子区基因多态性与其代谢表型的关系

目的 探讨中国人群高尿酸血症患者TNF-a启动子区-308位点多态性、-238位点基因多态性与HUA及其代谢表型的关联。方法 高尿酸血症患者188例，正常人51例，应用聚合酶链反应-限制性片段长度多态性分析方法，检测TNF-a基因启动子区-308G／A单核苷酸多态性位点基因型；尿酸酶法测血尿酸，葡萄糖氧化酶法测快速血糖。比色法测总胆固醇和甘油三酯，高密度脂蛋白胆固醇由选择性抑制法测定。上述化验均在血样提取后3h内完成。-20℃保存血样以便测定胰岛素浓度，免疫放射测定法测得胰岛素。随机选择高尿酸血症患者35例，正常人39例，同样方法检测TNF-a基因启动子区-238G／A单核苷酸多态性位点基因型及各生化指标。结果 对两位点单核苷酸多态性分析发现，高尿酸血症组-308位点AA＋GA分布频率（23．94％）明显高于对照组（11．76％）（P=0．0001）；-238位点的GG和GA基因型分布频率在两组之间无明显差异（P=0．08）。同时，-308位点的GA＋AA基因型组和GG型组相比，其中腰臀比、收缩期和舒张期血压、尿酸、甘油三酯差别均有统计学意义（P=O．05～0．01）；-238位点的两组基因型间各检测指标差别均无意义。结论 本研究结果显示HUA个体中TNF-Ot启动子区-308A携带者的基因型与高尿酸血症及其代谢表型有关。

The Relationship between the Gene Polymorphism of Tumor Necrosis Factor-a Promoter Region in Hyperuricemia Patients and its Metabolic Phenotype

Objectire To investigate the correlation between the -308 site, -238 site gene polymorphism of TNF-a promoter region in hyperuricemia and its metabolic phenotype. Methods HUA patients 188, normal people（NHU） 51, the -308G/A site single nueleotide polymorphism of TNF-a gene promoter region was decided by Polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） method. The level of serum uric acid is detected by uriease, blood glucose by glucose oxidase. Selective inhibition assay for total cholesterol, triglyeeride and high-density lipoprotein cholesterol. All these tests were completed within three hours after extraction. Keep blood samples at -20℃ to detect the concentration of insulin using immunoradiometric assay. HUA patients 35, NHU 39,the -238G/A site single nucleotide polymorphism of TNF-a gene promoter region was decided by the same method. Results By studying two single nucleotide polymorphism, the GA＋AA frequency of -308 site（23.94%） in HUA was significantly higher than NHU （11.76%）（P= 0.0001 ）; the genotype frequencies of GA and GG in -238 site had no significant difference between the two groups （P=0.08）. Meanwhile, comparing GA＋AA genotype and GG group of -308 site, waist-hip ratio,systolic and diastolic blood pressure, uric acid, triglycerides differences were statistically significant（P=O.05～O.O1）; the difference in -238 site between the two genotypes was no significance. Conclusion The results of this study show -308A carriers of TNF-a promoter region in HUA individual is correlated with hyperuricemia and its metabolic phenotype.