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.
Subject(s)
Humans , Arteries , Cerebrovascular Disorders , Follow-Up Studies , GTP Phosphohydrolases , Methods , MicroRNAs , Mortality , Odds Ratio , Pathology , Physiology , Polymorphism, Genetic , Prevalence , StrokeABSTRACT
OBJECTIVE: To identify the associations between polymorphisms of the 3′-untranslated region (UTR) of methylenetetrahydrofolate reductase (MTHFR) gene, which codes for an important regulatory enzyme primarily involved in folate metabolism, and idiopathic recurrent pregnancy loss (RPL) in Korean women. METHODS: The study population comprised 369 RPL patients and 228 controls. MTHFR 2572C>A, 4869C>G, 5488C>T, and 6685T>C 3′-UTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis or by TaqMan allelic discrimination assays. Natural killer cell proportions were determined by flow cytometry. RESULTS: The MTHFR 2572-5488-6685 (A-C-T) haplotype had an adjusted odds ratio of 0.420 (95% confidence interval, 0.178–0.994; p=0.048) for RPL. Analysis of variance revealed that MTHFR 4869C>G was associated with altered CD56⁺ natural killer cell percentages (CC, 17.91%±8.04%; CG, 12.67%±4.64%; p=0.024) and folate levels (CC, 12.01±7.18 mg/mL; CG, 22.15±26.25 mg/mL; p=0.006). CONCLUSION: Variants in the 3′-UTR of MTHFR are potential biomarkers for RPL. However, these results should be validated in additional studies of ethnically diverse groups of patients.