Cir Res：原发性高血压可能由母亲遗传

最新研究发现，原发性高血压可能来自于母亲的遗传缺陷。由浙江大学管敏鑫教授领衔的研究团队，与解放军总医院王士雯院士、美国辛辛那提儿童医院、奥地利维也纳医科大学进行合作，发现了由母系遗传的线粒体基因缺陷造成原发性高血压的致病机理。

据统计，我国患有高血压人数已达2亿，并以每年1000万新发人数递增，其中95%以上为原发性高血压。课题组通过对来自山西洪洞县一个原发性高血压家系进行普查，发现了典型的母系遗传特征：在这个祖孙5代共108人的大家族中，源于同一母性祖先的27个母系亲属成员中有15人的血压高于140/90 毫米汞柱，而81位非母系成员中仅有7人患有高血压。进一步研究表明，这部分患者的线粒体基因组发生了突变，造成线粒体呼吸链功能缺陷，能量供应不足，氧自由基水平升高，引发高血压。

这是世界上首次发现遗传性线粒体功能缺陷与高血压相关，从而诠释了母系遗传高血压的发病机制，为高血压的早期诊断、干预和防治提供了新的理论依据。此项成果将在3月31日出版的心血管领域的顶尖杂志——美国心脏协会会刊《循环研究》（Circulation Research）上发表。（生物谷Bioon.com）

生物谷推荐原文出处：

Circulation Research. 2011;108:862-870   doi: 10.1161/CIRCRESAHA.110.231811

Maternally Inherited Essential Hypertension Is Associated With the Novel 4263A>G Mutation in the Mitochondrial tRNAIle Gene in a Large Han Chinese Family

Shiwen Wang*, Ronghua Li, Andrea Fettermann, Zongbin Li, Yaping Qian, Yuqi Liu, Xinjian Wang, Anna Zhou, Jun Qin Mo, Li Yang, Pingping Jiang, Andreas Taschner, Walter Rossmanith, Min-Xin Guan*

Rational:Despite maternal transmission of hypertension in some pedigrees, pathophysiology of maternally inherited hypertension remains poorly understood.

Objective:To establish a causative link between mitochondrial dysfunction and essential hypertension.

Method and Results:A total of 106 subjects from a large Chinese family underwent clinical, genetic, molecular, and biochemical evaluations. Fifteen of 24 adult matrilineal relatives exhibited a wide range of severity in essential hypertension, whereas none of the offspring of affected fathers had hypertension. The age at onset of hypertension in the maternal kindred varied from 20 years to 69 years, with an average of 44 years. Mutational analysis of their mitochondrial genomes identified a novel homoplasmic 4263A>G mutation located at the processing site for the tRNAIle 5'-end precursor. An in vitro processing analysis showed that the 4263A>G mutation reduced the efficiency of the tRNAIle precursor 5'-end cleavage catalyzed by RNase P. tRNA Northern analysis revealed that the 4263A>G mutation caused 46% reduction in the steady-state level of tRNAIle. An in vivo protein-labeling analysis showed 32% reduction in the rate of mitochondrial translation in cells carrying the 4263A>G mutation. Impaired mitochondrial translation is apparently a primary contributor to the reductions in the rate of overall respiratory capacity, malate/glutamate-promoted respiration, succinate/glycerol-3-phosphate-promoted respiration, or N,N,N',N'-tetramethyl-p-phenylenediamine/ascorbate–promoted respiration and the increasing level of reactive oxygen species in cells carrying the 4263A>G mutation.

Conclusions:These data provide direct evidence that mitochondrial dysfunction caused by mitochondrial tRNAIle 4263A>G mutation is involved in essential hypertension. Our findings may provide new insights into pathophysiology of maternally transmitted hypertension.