两个携带线粒体tRNA^(Met)/tRNA^(Gln)A4401G和tRNA^(Cys)G5821A突变的中国汉族原发性高血压家系的临床及分子遗传学特征  

The mitochondrial tRNA^(Met)/tRNA^(Gln)A4401G and tRNA^(Cys)G5821A mutations may be associated with hypertension in two Han Chinese families

作　　者：许美芬[1,2] 何轶群[1,2] 耿军伟[1,2] 孟燕子[1,2] 于涵[1,2] 林枝[1,2] 施苏雪[1,2] 薛凌[1,2] 卢中秋[3] 管敏鑫[1,2,4] 

机构地区：[1]温州医科大学检验医学院、生命科学学院,温州325035 [2]温州医科大学浙江省医学遗传学重点实验室,温州325035 [3]温州医科大学附属第一医院急诊科,温州325000 [4]浙江大学遗传研究所,杭州310023

出　　处：《遗传》2014年第2期127-134,共8页Hereditas（Beijing)

基　　金：国家自然科学基金项目(编号:81070794,30971600);国家青年科学基金项目(编号:31100903);浙江省自然科学基金项目(编号:Y2110399);温州市瓯海区科技计划项目(编号:2011XM047);温州市瓯海区科技局社会发展科学研究项目(编号:20120177);浙江省大学生科技创新活动计划(新苗人才计划)项目(编号:2013R413045)资助

摘　　要：线粒体tRNA基因可能是原发性高血压发病相关的突变热点区域。文章报道了两个具有母系遗传特征的中国汉族原发性高血压家系的临床和分子遗传学特征。家系先证者和其他成员的临床数据表明,家系中母系成员高血压发病的严重程度存在差异,发病年龄也从36~79岁不等。对两个家系先证者使用24对有部分重叠的引物进行线粒体DNA全序列扩增分析,结果发现这两个先证者均携带同质性的tRNAMet/tRNAGlnA4401G和tRNACysG5821A突变,多态性变异位点都属于东亚单体型C。A4401G突变可能通过影响tRNAMet和tRNAGln前体的加工引起线粒体tRNA代谢水平的改变,而tRNACysG5821A突变位于tRNACys氨基酸受体臂,该突变使tRNACys氨基酸受体臂上原有的G6-C67配对消失,可能影响tRNACys空间结构和功能的稳定性,致使线粒体功能障碍。因此,tRNAMet/tRNAGlnA4401G和tRNACysG5821A突变可能是这两个原发性高血压家系的分子致病基础。Mitochondrial tRNA genes are the hot spots for mutations associated with essential hypertension. We report here the clinical and molecular genetic characterization of two Han Chinese pedigrees with materially inherited essential hypertension. Clinical evaluation revealed the variable severity and age-at-onset of hypertension among matrilineal relatives In particular, the age-at-onset of hypertension in the maternal kindred ranged from 36 years to 79 years. The sequence anal ysis of entire mitochondrial genome in two probands showed that two probands carded the identical homoplasmic tRNA^Met/tRNA^GlnA4401G and tRNA^CySGG5821A mutations and distinct sets of polymorphisms belonging to East Asian haplogroup C. The A4401G mutation may affect the processing of the precursors of tRNA^Met and tRNA^Gln, thereby altering the tRNA metabolism. The tRNA^Cys G5821A mutation is located in the acceptor stem of tRNA^Cys. This mutation may abol ish the predicted G6-C67 pairing and consequently affect the structure and stability of mitochondrial tRNAcys, thereby leading to mitochondrial dysfunction. Therefore, these data suggested that the tRNA^Met/tRNA^GlnA4401G and tRNA^Cys G5821A mutations are likely associated with essential hypertension in these two Chinese pedigrees.

关 键 词：原发性高血压 线粒体DNA 突变 单体型 

分 类 号：R394[医药卫生—医学遗传学] R544.11[医药卫生—基础医学]