原发性高血压患者发病与线粒体DNA控制区基因变异的关系

Relationship between attack of essential hypertension and gene variations in mitochondrial DNA control region

目的:探讨原发性高血压患者线粒体DNA控制区基因变异,并评估其在高血压发病中的作用。方法:提取符合WHO高血压诊断标准的20例原发性高血压患者和20例正常血压者的DNA。用3对交叉重叠引物扩增全部线粒体控制区D环基因,进行直接基因测序和对比分析。结果:原发性高血压患者线粒体D环控制区的变异频率及密度犤13.95个/例,0.19/(100个碱基·例)犦均高于正常血压组犤10.7个/例,0.14/(100个碱基·例犦χ2=11.84,P<0.01)。线粒体转录因子结)(合位点1区域呈高变异状态,而且存在部分微卫星区的不稳定,np152C及np16189C的多态性变化可能为高血压的高风险位点。结论:原发性高血压患者D环区基因高变异率,线粒体DNA控制区变异可能与高血压的发病存在密切的关联。

AIM: To explore the mitochondrial DNA (mtDNA) variations of D loop region in patients with essential hypertension (EH), and evaluate their roles in the pathogenesis of hypertension.METHODS: DNA was extracted from the 20 EH patients, who met the diagnostic standard of hypertension in WHO, and 20 normotensives. The entire genome of D loop region was amplified by using 3 overlapping primers, and direct gene sequence and comparative analysis were performed. RESULTS: The mtDNA variation frequency and density in D loop region of EH patients [13.95 per case, 0.19/100 base per case] were higher than those of normotensives [10.7 per case, 0.14/100 base per case](χ 2 =11.84, P< 0.01). There was higher variation frequency in mitochondrial transcription factor binding site 1 and mitochondrial microsatellite instability for EH patients. The polymorphism changes of np152C and np16189C were possibly the high risk sites susceptible to hypertension. CONCLUSION: EH patients have higher mtDNA variations rate in D loop region, which may be closely correlated with the pathogenesis of hypertension.