[Analysis of association of genetic polymorphisms of microRNAs with ischemic stroke]

Area of Science:

• Genetics
• Molecular Biology
• Epidemiology

Background:

• Ischemic stroke is a leading cause of disability and mortality worldwide.
• Genetic predisposition, including single nucleotide polymorphisms (SNPs), is increasingly recognized as a contributing factor to ischemic stroke susceptibility.
• MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been implicated in various diseases, including stroke.

Purpose of the Study:

• To investigate the association between specific SNPs in hsa-miR-196a2, hsa-miR-149, hsa-miR-146a, and hsa-miR-499 and the risk of developing ischemic stroke.
• To identify potential genetic biomarkers for ischemic stroke susceptibility.

Main Methods:

• Genotyping of four miRNA loci (hsa-miR-196a2, hsa-miR-149, hsa-miR-146a, hsa-miR-499) using Taqman-PCR and DNA sequencing.
• Case-control study design involving 510 ischemic stroke patients and 523 healthy controls.
• Statistical analysis to assess the association between genotypes and ischemic stroke, including stratified analysis based on risk factors.

Main Results:

• Common risk factors for ischemic stroke include smoking, diabetes, hypertension, high BMI, and abnormal serum lipids.
• The hsa-miR-146a rs2910164 polymorphism was significantly associated with ischemic stroke risk across multiple genetic models (codominant, dominant, recessive, allele).
• Stratified analysis revealed that the rs2910164 association was significant specifically in individuals who smoke and have hypertension. No significant associations were found for SNPs in hsa-miR-196a2, hsa-miR-149, or hsa-miR-499.

Conclusions:

• Smoking, diabetes, hypertension, and hyperlipidemia are confirmed risk factors for ischemic stroke.
• The hsa-miR-146a rs2910164 polymorphism is significantly associated with ischemic stroke susceptibility in the Dongyang population, particularly among those with smoking and hypertension.
• The G allele and GG/CG+GG genotypes of rs2910164 may contribute to ischemic stroke risk in this population, suggesting a potential role in disease pathogenesis.