Mitochondrial genome mutations in hypertensive individuals
Mitochondrial genome mutations in hypertensive individuals
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DOI：
10.1016/j.amjhyper.2004.02.020
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发表时间：
2004-07-01
影响因子：
3.2
通讯作者：
Gavras, H
中科院分区：
文献类型：
--
作者：
Schwartz, F;Duka, A;Gavras, H
人类原发性高血压（HTN）是一种病因不明的多基因、多因素和高度异质性疾病，在几项研究中已显示具有过度的母体传播，表明可能涉及线粒体。为了评估线粒体基因组对HTN的贡献，我们对高血压患者进行了系统的、扩展的筛查，以确定潜在的致病性mtDNA突变。我们将我们新开发的用于检测复杂疾病中线粒体突变的新型测试应用于来自波士顿医学中心HTN诊所确定的350个白色种族和98个非洲裔美国人种族的高血压数据集，并确定了可能涉及线粒体的家庭。我们分析了来自20个这样的家系的先证者的整个线粒体基因组的序列，包括10个非洲裔美国人和10个白色家庭。与参考“剑桥”序列的比较显示，共有297个碱基的变化，包括24个在核糖体RNA（rRNA）基因，15个在转移RNA（tRNA）基因，和46个氨基酸的取代，其余涉及非编码区或同义的变化。在编码区突变中，30个是新的，13个高血压先证者携带至少一个新的变体，通常与先前描述的常见多态性相结合，其中几个与心血管和肾脏病理相关。这些数据将作为大规模病例对照关联研究的起点。(C)2004年美国高血压杂志有限公司
Human essential hypertension (HTN), a polygenic, multifactorial, and highly heterogeneous disorder of unknown etiology, has been shown to have excess maternal transmission in several studies, suggesting a possible mitochondrial involvement. In an effort to assess the contribution of the mitochondrial genome to HTN we initiated a systematic, extended screening of hypertensive individuals to identify potentially pathogenic mtDNA mutations. We applied our newly developed novel class of tests for the detection of mitochondrial mutation involvement in complex diseases to the hypertension data set from 350 pedigrees of white ethnicity and 98 of African American ethnicity ascertained at HTN clinics associated with Boston Medical Center, and we identified families with a likely mitochondrial involvement. We analyzed the sequence of the entire mitochondrial genome in probands from 20 such pedigrees, consisting of 10 African American and 10 white families. Comparison with the reference "Cambridge" sequence revealed a total of 297 base changes, including 24 in the ribosomal RNA (rRNA) genes, 15 in the transfer RNA (tRNA) genes, and 46 amino acid substitutions, with the remainder involving the noncoding regions or synonymous changes. Among the coding region mutations, 30 are novel, with 13 hypertensive probands carrying at least one novel variant, usually in combination with the previously described common polymorphisms, several of which are associated with cardiovascular and renal pathologies. These data will serve as a starting point for large-scale case-control association studies. (C) 2004 American Journal of Hypertension, Ltd.