Genetic Polymorphisms in Pre-microRNAs and Risk of Ischemic Stroke in a Chinese Population

Abstract

Ischemic stroke is considered to be a complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. MicroRNAs participated in various physiopathological processes; common single-nucleotide polymorphisms (SNPs) in pre-miRNAs have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of the hsa-mir-196-a2/rs11614913 T/C, hsa-mir-146a/rs2910164 C/G, and hsa-mir-499/rs3746444 A/G polymorphisms in pre-miRNAs with the risk of ischemic stroke in a Chinese population. The three polymorphisms were identified in 296 ischemic stroke patients and 391 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. The frequency of the allele G of hsa-mir-499/rs3746444 A/G showed significant association with ischemic stroke when compared with controls (OR = 1.509, 95%CI = 1.151-1.978, P = 0.003). Increased ischemic stroke risks were associated with rs3746444 A/G genotypes in different genetic model (homozygote comparison: P = 0.045, OR = 2.084, 95%CI = 1.019-4.262; heterozygote comparison: P = 0.024, OR = 1.489, 95%CI = 1.063-2.087; dominant genetic model: P = 0.007, OR = 1.563, 95%CI = 1.135-2.153). Similar results were obtained by adjusted fully risk factors. However, we failed to find any association between the alleles and genotypes of rs2910164 C/G and rs11614913 T/C SNPs and ischemic stroke, respectively (p > 0.05). The present study provided evidence that hsa-mir-499/rs3746444 A/G polymorphism might be associated with a significantly increased risk of ischemic stroke in a Chinese population, indicating that the common genetic polymorphism in pre-microRNAs contributed to the pathogenesis of ischemic stroke.

Association of the Genetic Polymorphisms in Pre-MicroRNAs with Risk of Ischemic Stroke in a Chinese Population

“…miR-196a2 and miR-499 could regulate annexin A1[ 15 ] and CRP [ 16 ], which are also the general causes of cerebral ischemia [ 27 , 28 ] and associated with elevated blood pressure, BMI, insulin resistance, and triglycerides [ 29 ]. We found no association between miR-196a2/rs11614913, miR-499/rs3746444 and ischemic stroke in this study, although Liu et al reported that miR-499 G allele was significantly associated with increased risk of ischemic stroke in Chinese population [ 30 ]. These two SNPs have also been widely studied in other human diseases, including congenital heart disease [ 31 ], coronary heart disease [ 13 ] and cancer [ 12 ].…”

A single nucleotide polymorphism located in microRNA-499a causes loss of function resulting in increased expression of osbpl1a and reduced serum HDL level

“…miR-499 and miR-196a2 modulated CRP and Annexin A1, which are also the common contributors to cerebral ischemia and related to increased triglycerides, insulin resistance, BMI and blood pressure (36)(37)(38)(39). Although Liu et al reported that miR-499 G allele was significantly associated with increased risk of ischemic stroke in Chinese population, we found that miR-499/ rs3746444 and miR-196a2/rs11614913 were not related to ischemic stroke in this study (40). These two SNPs have also been extensively investigated in other human disorders, such as cancer, coronary heart disease and congenital heart disease (41)(42)(43).…”

Association between miR-499 rs3746444 polymorphism and ischemic stroke : A systematic review and meta-analysis

“…A total of six studies [10,12,[16][17][18][19] , involving 2569 IS cases and 2645 controls, were included in this metaanalysis. The characteristics of the included studies was shown in table1.…”