线粒体转运RNA基因突变与原发性高血压的相关研究

Correlation analysis between mitochondrial DNA mutation and essential hypertension

摘要:

目的 探究线粒体转运RNA(tRNA)基因突变与母系遗传原发性高血压(EH)的关联性。方法 依据EH诊断和母系遗传判别标准,筛选2015年1月至2018年12月解放军总医院心血管内科收治的母系遗传EH患者17例(A组)、非母系遗传EH患者65例(B组)。选取同期来院进行健康体检的正常对照人群33名(C组)。对全线粒体DNA(mtDNA)进行测序并与线粒体基因文库MitoMap的修正剑桥序列进行比对,分析3组受试者线粒体tRNA基因突变率差异及其与母系遗传EH发生的关系。应用SPSS 19.0软件对数据进行分析。结果 纳入人群中母系遗传EH占总EH 20.7%(17/82)。mtDNA序列对比分析发现,与C组(0.04%)比较,A组(0.28%,P=0.024)及B组(0.12%,P=0.046)患者线粒体tRNA基因总变异率明显升高,但A与B组间比较差异无统计学意义(P=0.076)。对A组患者进一步分析显示,仅有1个线粒体tRNA基因位点突变的先证者A06、A11和A13所在3个家系分别发生mtDNA A5823G、mtDNA T4386C与mtDNA C15910T突变,三个家系母系成员EH发病率分别为53.8%(7/13)、87.5%(7/8)和75.0%(9/12),发病率均较高,提示这3个位点突变可能与母系遗传EH发生密切关联。另外,mtDNA 5597缺失在A组(4例,23.5%)、B组(14例,21.5%)和C组(1例,3.0%)均出现。与C组比较,A组(P=0.002)与B组(P=0.002)患者mtDNA 5597缺失率均显著升高,但A组与B组间比较差异无统计学意义(P=0.127)。结论 mtDNA A5823G、mtDNA T4386C与mtDNA C15910T突变与母系遗传EH有较好的关联性,但mtDNA 5597缺失与母系遗传EH关系不大。

Abstract:

Objective To explore the relationship between mutations of mitochondrial transfer RNA (tRNA) gene and maternal essential hypertension (EH). Methods According to the criteria of EH diagnosis and maternal inheritance discrimination, 17 patients with maternal inheritance EH (group A) and 65 patients with non-maternal inheritance EH (group B) were screened out from our hospital during January 2015 to December 2018. Thirty-three healthy individuals who took physical examination in our hospital during the same period were also subjected as control group. The whole mitochondrial DNA (mtDNA) was sequenced and compared with the modified Cambridge sequence of MitoMap. The mutation rate of mitochondrial tRNA gene and its relationship with maternal inheritance EH were analyzed in the 3 groups. SPSS statistics 19.0 was used for data analysis. Results The subject with maternal EH accounted for 20.7% (17/82) of the EH population screened. Compared with control group (0.04%), the total variation rate of mito-chondrial tRNA gene was significantly higher in group A (0.28%, P=0.024) and group B (0.12%, P=0.046), but there was no significant difference between group A and group B (P=0.076). Further analysis for group A showed that only one mitochondrial tRNA locus mutation in probands A06, A11 and A13 occurred mtDNA A5823G, mtDNA T4386C and mtDNA C15910T mutations in 3 families respectively. The incidence of EH in maternal members of 3 families was 53.8%(7/13), 87.5%(7/8) and 75.0%(9/12), respectively. The incidence of EH was high, suggesting that the mutations at these 3 loci might be closely related to maternal EH. In addition, mtDNA 5597 deletions were found in group A (4 cases, 23.5%), group B (14 cases, 21.5%) and control group (1 case, 3.0%). Compared with control group, the deletion rate of mtDNA 5597 was significantly higher in group A (P=0.002) and group B (P=0.002), but there was no significant difference between group A and group B (P=0.127). Conclusion The mutations of mtDNA A5823G, mtDNA T4386C and mtDNA C15910T are closely related to maternal inheritance EH but the deletion of mtDNA 5597 was not related to maternal EH.