J Stroke.  2018 Jan;20(1):110-121. 10.5853/jos.2017.02586.

Association of MicroRNA Biogenesis Genes Polymorphisms with Ischemic Stroke Susceptibility and Post-Stroke Mortality

Affiliations
  • 1Department of Biomedical Science, CHA University College of Life Science, Seongnam, Korea. nkkim@cha.ac.kr
  • 2Department of Emergency Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
  • 3Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, Korea. okjun77@cha.ac.kr
  • 4Department of Neurosurgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
  • 5Department of Internal Medicine, CHA University, Seongnam, Korea.

Abstract

BACKGROUND AND PURPOSE
MicroRNA (miRNA) expression has been examined in multiple conditions, including various cancers, neurological diseases, and cerebrovascular diseases, particularly stroke. Existing evidence indicates that miRNA biosynthesis and function play crucial roles in ischemic stroke physiology and pathology. In this study, we selected six known polymorphisms in miRNA-biogenesis genes; DICER rs13078A>T, rs3742330A>G; DROSHA rs10719T>C, rs6877842G>C; Ran GTPase (RAN) rs14035C>T; exportin 5 (XPO5) rs11077A>C.
METHODS
We analyzed the associations between these polymorphisms and disease status and clinical factors in 585 ischemic stroke patients and 403 controls. Genotyping was performed with the polymerase chain reaction-restriction fragment length polymorphism method.
RESULTS
The DICER rs3742330A>G (AA vs. AG+GG: adjusted odds ratio [AOR], 1.360; 95% confidence interval [CI], 1.024 to 1.807; P=0.034) and DROSHA rs10719T>C polymorphisms (TT vs. CC: AOR, 2.038; 95% CI, 1.113 to 3.730; P=0.021) were associated with ischemic stroke prevalence. During a mean follow-up of 4.80±2.11 years, 99 (5.91%) of the stroke patients died. In multivariate Cox proportional hazard regression models, a significant association was found between RAN rs14035 and survival of large artery disease patients with ischemic stroke (CC vs. TT: adjusted hazard ratio, 5.978; P=0.015).
CONCLUSIONS
An association was identified between the DICER and DROSHA polymorphisms and ischemic stroke. Specifically, polymorphisms (rs3742330 and rs10719) were more common in stroke patients, suggesting that they may be associated with an increased risk of ischemic stroke.

Keyword

Polymorphism, genetic; Stroke; MicroRNA biogenesis genes; Mortality

MeSH Terms

Arteries
Cerebrovascular Disorders
Follow-Up Studies
GTP Phosphohydrolases
Humans
Methods
MicroRNAs*
Mortality*
Odds Ratio
Pathology
Physiology
Polymorphism, Genetic
Prevalence
Stroke*
GTP Phosphohydrolases
MicroRNAs
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