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 miR- 146a was significantly more frequent in ACI patients who were ApoEε4 (+) carriers (p=0.0233), and rs2910164 G>C was intimately associated with the ApoEε4-containing genotype in patients compared with the ApoEε4 (-) carriers (p=0.0323). Conclusions: Our findings indicated that the C allele of rs2910164 miR-146a is an important risk factor for ACI, and ApoEε4 may function through attenuating miR-146a expression to enhance ACI susceptibility. This study provides new information about the possible relationship between miR- 146a and ApoEε4 in the development of ACI, with potentially important therapeutic implications.