Apolipoprotein E Epsilon 4 Enhances the Association between the rs2910164 Polymorphism of miR-146a and Risk of Atherosclerotic Cerebral Infarction

Abstract

Aim: To analyse the relationship between two potentially functional single-nucleotide polymorphisms (SNPs) of the miR-146a gene (rs2910164 and rs57095329) and the risk of atherosclerotic cerebral infarction (ACI).Methods: A total of 297 patients with ACI and 300 matched healthy individuals were enrolled in the study. The miR-146a polymorphism was detected using the polymerase chain reaction -restriction fragment length polymorphism method. Results: A significant difference in the C allele frequency at rs2910164 (p 0.028) was noted between patients with ACI and control subjects. In contrast, the genotype and allele frequencies of rs57095329 were not statistically associated with ACI. In addition, the decreased expression of miR146a was significantly more frequent in ACI patients who were ApoE 4 ( ) carriers (p 0.0233), and rs2910164 G C was intimately associated with the ApoE 4-containing genotype in patients compared with the ApoE 4 ( ) carriers (p 0.0323). Conclusions: Our findings indicated that the C allele of rs2910164 miR-146a is an important risk factor for ACI, and ApoE 4 may function through attenuating miR-146a expression to enhance ACI susceptibility. This study provides new information about the possible relationship between miR146a and ApoE 4 in the development of ACI, with potentially important therapeutic implications.

Association between polymorphisms in microRNAs and ischemic stroke in an Asian population: evidence based on 6,083 cases and 7,248 controls

“…Our meta-analysis, in contrast, suggests that this C allele is not significantly associated with IS risk; instead, we found the GG genotype of miR-146a (rs2910164) to be associated with increased risk. Our result may be more reliable than that of the previous meta-analysis by Zhu et al 39 because our meta-analysis contained nine more case–control studies 14 , 15 , 17 , 21 – 26 with larger samples. Our subgroup analysis suggesting a significant relationship between the C allele of miR-146a (rs2910164) and lower IS risk contained only one case–control study, which was by Jeon et al 16 …”

Inflammation‐regulatory microRNAs: Valuable targets for intracranial atherosclerosis

“…Yet, the multiple roles of miRNAs in modulating ICAS progression may make it difficult to illuminate the exact mechanisms (Figure ). Besides, consideration of other factors that control miRNA regulation in ICAS, such as single nucleotide polymorphisms (Zhong et al, ) and lncRNAs (Huang, Wang, Mao, & Nan, ), may spread wider net of miRNA‐inflammation‐ICAS pathways. Future clinical researches with a larger scale and a higher power are still required to improve the precision of exploring miRNAs in patients with ICAS, so as to gain a better understanding of ICAS pathophysiology.…”

The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population

“…In addition, the presence of ε2 has been associated with lower LDL-C level but with no in uence on HDL-C level [34]. Another study showed that the C allele of SNP rs2910164 of the miR-146a gene is a risk factor for atherosclerotic cerebral infarction (ACI) and that APOE ε4 may enhance ACI susceptibility by reducing miR-146a expression [36].…”