宁夏地区高血压肾损害患者肿瘤坏死因子-α-308基因多态性及其与贝那普利治疗反应的相关性研究

摘要

目的 阐明肿瘤坏死因子-α(TNF-α)-308基因多态性与宁夏地区高血压肾损害之间,及其与贝那普利治疗反应的相关性.方法 选取284例初诊高血压病患者,通过检测尿蛋白排泄率明确高血压肾损害,同时选取160例健康体检者作为正常血压对照组.所有入选对象留取血浆标本,检测TNF-α水平及其TNF-α-308基因多态性.再以贝那普利作为降压药物之一对高血压肾损害患者进行干预,观察TNF-α-308不同基因型对贝那普利的治疗反应,并进行比较分析.结果 单纯高血压病患者的TNF-α-308以GA基因型为多见,其次为GG、AA,G/A等位基因频率分别为53％/47％.高血压肾损害患者的TNF-α-308以GG基因型最为多见,其次为GA和AA,G/A等位基因频率分别为70％/30％,基因型及G/A等位基因频率比较差异有统计学意义(P＜0.05).TNF-α-308的AA基因型贝那普利治疗前后尿蛋白排泄率和TNF-α的改变幅度最大,其次是GA和GG基因型,3组间比较差异有统计学意义(P＜0.05).结论 TNF-α-308基因与高血压肾损害及其对贝那普利治疗的反应相关.%Objective To study the correlation between the genetic polymorphism of tumor necrosis factor-α(TNF-α)-308 with benazepril treatment response in the patients with hypertensive renal damage in Ningxia area.Methods Two hundred and eighty-four patients initially diagnosed as hypertension were enrolled and the hypertensive renal damage defined by the measurement of urinary albumin excretion rate(UAER).At the same time 160 individuals undergoing healthy physical examination were selected as the normal blood pressure control group.The plasma samples were obtained from all the subjects,and plasma level of TNF-α and TNF-α-308 gene polymorphism were detected.Then the patients with hypertensive renal damage were interfered with benazepril as one of the antihypertensive drugs,and the treatment response of different TNF-α-308 genotypes to benazepril was observed,and the comparative analysis was performed.Results Among the TNF-α-308 genotypes in the patients with simple hypertension,genotype GA was the most common,followed by GG and AA successively,with the G/A allele frequency of 53 ％/47 ％ (P＜0.05).In the patients with hypertensive renal damage,genotype GG was the most common,followed by GA and AA successively,with the G/A allele frequency of 70％/30％,the genotypes and allele frequency had no statistical difference(P＜0.05).Before and after benazepril treatment,the change range of UAER in the patients with genotype AA was maximal,followed by the genotype GA and GG,the difference among 3 groups was statistically significant(P＜0.05).Conclusion The TNF-α-308 gene is correlated with hypertensive renal damage and its response to benazepril treatment.