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

Abstract

Background and PurposeMicroRNA (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. MethodsWe 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. ResultsThe 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). ConclusionsAn 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.

The effects of DICER1 and DROSHA polymorphisms on susceptibility to recurrent spontaneous abortion

“…Several studies have found the relationship between DICER1 and DROSHA polymorphisms and several diseases, but the published reports on their impacts on RSA are rare …”

“…Considering the role of genetic variants in pathogenesis of multifactorial diseases, numerous studies have evaluated the effects of miRNA and miRNA biosynthesis machinery polymorphisms on their pathogenesis . DROSHA and DICER1 genes are located on chromosomes 5 and 14, respectively .…”

“…DROSHA and DICER1 genes are located on chromosomes 5 and 14, respectively . There are several single nucleotide polymorphisms (SNPs) in DROSHA and DICER1 genes, and their effects on various diseases have been investigated …”

“…13 Considering the role of genetic variants in pathogenesis of multifactorial diseases, numerous studies have evaluated the effects of miRNA and miRNA biosynthesis machinery polymorphisms on their pathogenesis. [14][15][16] DROSHA and DICER1 genes are located on chromosomes 5 and 14, respectively. 17,18 There are several single nucleotide polymorphisms (SNPs) in DROSHA and DICER1 genes, and their effects on various diseases have been investigated.…”

“…17,18 There are several single nucleotide polymorphisms (SNPs) in DROSHA and DICER1 genes, and their effects on various diseases have been investigated. 16,19 Two other studies demonstrated that the combination of DROSHA and DICER1 polymorphisms could increase RSA risk. 20,21 To date, very few studies have been conducted on the effects of DROSHA and DICER1 polymorphisms on RSA.…”