Mitochondrial tRNA variants in Chinese subjects with coronary heart disease.
BACKGROUND
Coronary heart disease is the leading cause of death worldwide. Mitochondrial genetic determinants for the development of this disorder remain less explored.


RESULTS
We performed a clinical and genetic evaluation and mutational screening of 22 mitochondrial tRNA genes in a cohort of 80 genetically unrelated Han Chinese subjects and 125 members of 4 families with coronary heart disease and 512 Chinese 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 tRNAs by these mtDNA mutations caused mitochondrial dysfunction. These may be the first evidence that mtDNA mutations increase the risk of coronary heart disease. Our findings may provide new insights into the pathophysiology of this disorder.
Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
Yanwen
Y
Qin
Ling
L
Xue
Pingping
P
Jiang
Meifen
M
Xu
Yiqun
Y
He
Suxue
S
Shi
Yangyiyi
Y
Huang
Jiqiang
J
He
Jun Qin
JQ
Mo
Min-Xin
MX
Guan
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003327:Coronary Disease / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012343:RNA, Transfer / Q000235:genetics*; D012307:Risk Factors
D004272:DNA, Mitochondrial; D012343:RNA, Transfer
coronary heart disease; maternal transmission; mitochondrial tRNA; mutation