The ANRIL Genetic Variants and Their Interactions with Environmental Risk Factors on Atherothrombotic Stroke in a Han Chinese Population

Abstract

Ischemic stroke (IS) is considered to be a heterogeneous, multifactorial disease with a strong genetic background. This study aims to determine whether variants in the antisense noncoding RNA in the INK4 locus (ANRIL) gene are associated with IS in Han Chinese, as well as whether there is evidence of a gene-environment interactions. A case-controlled association study was conducted in which only patients with atherothrombotic stroke (ATS) were enrolled. Multifactor dimensionality reduction model was employed to screen the best interaction combinations among gene and environmental risk factors; RESULTS: A total of 405 subjects (200 cases and 205 controls) and 16 single nucleotide polymorphisms (SNPs) in ANRIL gene were included in this study. The 4 SNPs (rs1537378, rs2184061, rs7044859, and rs7865618) were found to be significantly related to ATS in Chinese Han nationality. In overall people or subjects aged 45 years or older, the GG genotype and G allele of rs1537378, the AA genotype and A allele of rs2184061 and rs7865618, and the AA genotype of rs7044859 increased the risk of ATS. In males, the GG genotype and G allele of rs1537378, the AA genotype and A allele of rs7865618, and the A allele of rs2184061 conferred a susceptibility to ATS. Additionally, the AAAGAGCAAAAAATAG haplotype exhibited an elevated risk of ATS, and a significant interaction was found in ATS susceptibility between ANRIL gene and dyslipidemia; CONCLUSIONS: The ANRIL gene was related to ATS susceptibility in a Han Chinese. Future studies should be performed with larger samples and among different ethnic populations.