title: Mitochondrial genome mutations in hypertensive individuals.
abstract: 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.
authors.affiliation: Department of Medicine, Genetics Program, Boston University School of Medicine, Boston, Massachusetts 02118, USA. fschw@bu.edu
authors.forename: Faina
authors.initials: F
authors.lastname: Schwartz
authors.forename: Arvi
authors.initials: A
authors.lastname: Duka
authors.forename: Fengzhu
authors.initials: F
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Athanasios
authors.initials: A
authors.lastname: Manolis
authors.forename: Haralambos
authors.initials: H
authors.lastname: Gavras
mesh_terms: D044383:Black People / Q000235:genetics; D001900:Boston; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human; D006115:Greece; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012335:RNA, Ribosomal / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; D012343:RNA, Transfer