Open AccessMitochondrial tRNA Variants in C hinese Subjects With Coronary Heart Disease
Author(s) -
Qin Yanwen,
Xue Ling,
Jiang Pingping,
Xu Meifen,
He Yiqun,
Shi Suxue,
Huang Yangyiyi,
He Jiqiang,
Mo Jun Qin,
Guan MinXin
Publication year - 2014
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.113.000437
Subject(s) - genetics , transfer rna , mitochondrial dna , mutation , medicine , gene , mitochondrial disease , pedigree chart , non mendelian inheritance , biology , rna
Background Coronary heart disease is the leading cause of death worldwide. Mitochondrial genetic determinants for the development of this disorder remain less explored. Methods and Results We performed a clinical and genetic evaluation and mutational screening of 22 mitochondrial tRNA genes in a cohort of 80 genetically unrelated Han C hinese subjects and 125 members of 4 families with coronary heart disease and 512 C hinese control subjects. This analysis identified 16 nucleotide changes among 9 tRNA genes. Of these, the T5592C mutation creates a highly conservative base pairing (5G‐68C) on the acceptor stem of tRNA Gln , whereas the G15927A mutation destabilizes a highly conserved base pairing (28C‐42G) in the anticodon stem of tRNA Thr . However, the other tRNA variants were polymorphisms. The pedigrees of BJH24 carrying the T5592C mutation, BJH15, and BJH45 harboring the G15927A mutation exhibited maternal transmission of coronary heart disease. Sequence analysis of their mitochondrial genomes revealed the presence of T5592C or G15927A mutation but the absence of other functionally significant mutations in all matrilineal relatives of these families. Conclusions Our previous observations showed that altered structures of tRNA s by these mt DNA mutations caused mitochondrial dysfunction. These may be the first evidence that mt DNA mutations increase the risk of coronary heart disease. Our findings may provide new insights into the pathophysiology of this disorder.