三个携带线粒体DNA tRNAGln 4363TC突变的中国汉族原发性高血压家系临床及遗传特征分析

doi:10.3969/j.issn.2095-9400.2015.05.001

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题名	三个携带线粒体DNA tRNAGln 4363TC突变的中国汉族原发性高血压家系临床及遗传特征分析
其他题名	The genetic analysis of mitochondrial tRNAGln 4363 T C mutation associated with essential hypertension in three Chinese Han pedigrees
作者	于涵 1,3,4; 耿军伟 1,3,4; 林枝 1,3,4; 薛凌1,3,4; 唐霄雯1,3,4; 郑斌娇 1,3,4; 吕建新1,3,4; 卢中秋1,2,3,4; 管敏鑫1,3,4
发表日期	2015
发表期刊	温州医科大学学报影响因子和分区
语种	中文
原始文献类型	Periodical
关键词	原发性高血压线粒体DNA tRNAGln 基因突变汉族
其他关键词	essential hypertension ; mitochondrial DNA ; tRNAGln ; gene mutations ; Han pedigress
摘要	目的:通过对3个携带tRNAGln 4363TC突变的原发性高血压家系进行临床、遗传和分子特征分析评估,探讨线粒体tRNAGln 4363TC突变在母系遗传原发性高血压发生发展中的作用.方法:PCR扩增848例原发性高血压患者和254例正常对照样本线粒体tRNA基因,对携带tRNAGln 4363TC突变的3个家系进行家系及线粒体基因相关分析.结果:共发现3例患者携带tRNAGln 4363TC突变,突变率为0.35%,患者家系中共有母系成员28位,其中12位患有不同程度的高血压,发病年龄从27到64岁,平均发病年龄为44岁,有1位非母系成员患病,母系成员中男性患者的后代均未表现出发病.3位先证者的线粒体基因全序列分析结果显示,除同质性tRNAGln 4363TC突变外,还有64个多态性位点,分别属于东亚线粒体单体型Z3、Z3和B4d.tRNAGln 4363T位点在进化上高度保守,该位点对应tRNAGln二级结构反密码子环的A38位,tRNAGln 4363TC突变可能影响此位点与反密码子识别功能的高保真性和正常tRNA结构的形成及结构的稳定性.结论:3个携带tRNAGln 4363TC突变的中国汉族原发性高血压家系母系遗传特征明显,线粒体tRNAGln 4363TC突变可能是这3个原发性高血压家系发病的主要分子基础.3个携带线粒体tRNAGln 4363TC突变的原发性高血压家系表现出的同质性突变、发病年龄及外显率不同等表型差异特征提示核修饰基因、环境因素和线粒体遗传背景等可能对tRNAGln 4363TC突变家系原发性高血压的表型表达有一定的影响.
其他摘要	Objective: To analyze and evaluate the clinical, genetic and molecular characteristics of mtDNA in three Han Chinese pedigrees with essential hypertension and explore the role of tRNAGln 4363TC mutation in the development of those maternally inherited essential hypertension.Method: Mitochondrial tRNA gene of 848 Chinese Han essential hypertension subjects and 254 control subjects were ampliifed with PCR. Members of 3 Chinese Han pedigrees with mitochondrial tRNAGln 4363TC mutation underwent mitochondrial DNA ge-netic analysis and pedigree assessment.Result: Three essential hypertension subjects were found with tRNAGln 4363TC mutation, and with variable severity and age-of-onset in hypertension among the three pedigrees. The percentage of this mutation was 0.35%. Twelve of 28 matrilineal relatives in these families exhibited the variable degree of hypertension at the age at onset of 27 to 64 years old and at the average of 44 years old, while none of the offspring at affected father had hypertension. Sequence analysis of complete mitochondrial genomes in 3 pedi-grees showed that, in addition to the homoplasmic 4363TC mutation, there were also 64 other mutations, and the mtDNA polymorphisms belonged to haplogroups Z3, Z3 and B4d, respectively. The tRNAGln 4363T was localized at immediately 3'end to the anticodon, corresponding to highly conserved adenine at position 38 of tRNAGln, the4363CT mutation might affect the high ifdelity of recognition and the formation and stability of normal tRNA structure.Conclusion: The occurrence of the tRNAGln 4363TC mutation in three genetically unrelated pedigrees affected by hypertension and the absence in 254 Chinese controls strongly indicate that this mutation is associated with essential hypertension. The homoplasmic form, late onset and incomplete penetrance of hypertension ob-served in those Chinese pedigrees suggest that tRNAGln 4363TC mutation may be insufifcient to produce a clini-cal phenotype, nuclear modiifer gene (s) or environmental factor (s) may play a role in the phenotypic expression of essential hypertension related to tRNAGln 4363TC mutation.
资助项目	国家青年科学基金资助项目;浙江省卫生厅医药卫生科学研究基金资助项目;温州医学院科研发展基金资助项目;浙江省自然科学基金资助项目;
ISSN	2095-9400
卷号	45 期号:5 页码:313-320
DOI	10.3969/j.issn.2095-9400.2015.05.001
页数	8
收录类别	万方 ; ISTIC
URL	查看原文
社科自定义期刊分类	G类
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/141396
专题	附属第一医院检验医学院（生命科学学院、生物学实验教学中心）附属第一医院_急诊科
作者单位	1.温州医科大学 Attardi线粒体生物医学研究院,浙江温州,325035; 2.温州医科大学附属第一医院急诊科,浙江温州,325015; 3.温州医科大学 Attardi线粒体生物医学研究院,浙江温州 325035; 4.浙江大学遗传研究所,浙江杭州 310058
第一作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	于涵,耿军伟,林枝,等. 三个携带线粒体DNA tRNAGln 4363TC突变的中国汉族原发性高血压家系临床及遗传特征分析[J]. 温州医科大学学报,2015,45(5):313-320.
APA	于涵., 耿军伟., 林枝., 薛凌., 唐霄雯., ... & 管敏鑫. (2015). 三个携带线粒体DNA tRNAGln 4363TC突变的中国汉族原发性高血压家系临床及遗传特征分析. 温州医科大学学报, 45(5), 313-320.
MLA	于涵,et al."三个携带线粒体DNA tRNAGln 4363TC突变的中国汉族原发性高血压家系临床及遗传特征分析".温州医科大学学报 45.5(2015):313-320.