Byoung Soo Shin

Association of the miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms With Ischemic Stroke and Silent Brain Infarction Risk

Objective—MicroRNAs play a role in atherosclerosis-related diseases, such as cerebrovascular or cardiovascular disease. However, the effect of miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms on stroke and silent brain infarction (SBI) susceptibility has not been reported. Methods and Results—Using polymerase chain reaction-amplified DNA, microRNA polymorphisms were analyzed in 678 patients with ischemic stroke, 373 patients with SBI, and 553 control subjects. The miR-146aC>G polymorphism and miR-146aG/-149T/-196a2C/-499G allele combination was significantly associated with ischemic stroke prevalence. For SBI prevalence, there were no statistically significant genetic markers. However, some allele combinations were associated with increased SBI incidence (C-T-C-G and G-T-T-A of miR-146a/-149/-196a2/-499). In subgroup analyses, miR-146aC>G increased stroke risk in female, normotensive, and nondiabetic groups. There were significant combined effects between microRNA polymorphisms and homocysteine/folate levels on ischemic stroke and SBI prevalence. Conclusion—The miR-146aG allele and miR-146aG/-149T/-196a2C/-499G allele combination were associated with ischemic stroke pathogenesis. The combined effects between microRNA polymorphisms and homocysteine/folate levels may contribute to stroke and SBI prevalence.

Association between common genetic variants of α2A-, α2B- and α2C-adrenoceptors and the risk of silent brain infarction.

Silent brain infarction (SBI) is an asymptomatic cerebrovascular disorder. The aim of the present study was to investigate the association between adrenoceptor-α2 (ADRA2) gene polymorphisms and SBI. A total of 361 patients with SBI and 467 healthy control subjects were examined. The polymerase chain reaction was performed to genotype the ADRA2A 1780G>A, ADRA2B 301-303 insertion/deletion (I/D) and ADRA2C 322-325I/D polymorphisms. The frequency of the ADRA2C 322-325I/D polymorphism was significantly different between patients with SBI and control subjects. When interaction analyses were performed for vascular risk factors, the ADRA2C 322-325ID genotype increased the risk for SBI in the presence of hypertension and elevated plasma homocysteine levels. The ADRA2C 322-325ID genotype and plasma homocysteine levels showed a significant synergistic effect for SBI. In addition, the ADRA2A 1780AA genotype was associated with elevated plasma homocysteine levels. Although further analysis of the association between ADRA2 polymorphisms and clinical risk factors of SBI is required, the present study of a limited set of SBI risk factors with ADRA2 polymorphisms provides the first evidence of the involvement of ADRA2 gene family members in the development of SBI. Further studies using larger and more heterogeneous populations are required to validate the association of ADRA2 polymorphisms with SBI.