Published in:
01-10-2018 | Original Article
Allele-specific methylation contributed by CpG-SNP is associated with regulation of ALOX5AP gene expression in ischemic stroke
Authors:
Yunshu Shi, Liyan Xu, Qingchuan Feng, Aifan Li, Jing Jia, Yan Xu, Dongzhi Yang, Yuchao Zhang, Xuran Zhang, Huiling Zhao, Jun Wang, Ying He, Hong Zheng
Published in:
Neurological Sciences
|
Issue 10/2018
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Abstract
Previous studies have shown that CpG-SNPs might have influence on gene function via allele-specific DNA methylation (ASM). However, association study between DNA methylation and the promoter CpG-SNPs in ALOX5AP gene with IS has not been reported. The present study aims to explore the relationship among CpG-SNPs, methylation levels, and messenger RNA (mRNA) expression levels of ALOX5AP gene. Firstly, we made a two-stage association study to identify a potential associated CpG-SNP (rs4073259) by SNaPshot genotyping approach (P = 0.015, OR = 0.672, 95% CI 0.487–0.927; P = 0.035, OR = 0.809, 95% CI 0.664–0.985, respectively). In addition, the methylation levels of 17 CpG sites located in the promoter of ALOX5AP were tested by MethylTarget sequencing. The methylation level of GG genotype carriers is significantly higher than those with the AG and AA genotypes (P < 0.05). And the GG genotype carriers with higher DNA methylation levels have a decreased mRNA expression levels of ALOX5AP (P < 0.05). Finally, we found that the G allele with higher methylation level has got a lower transcription activity than the A allele by luciferase assay (P = 0.000).The study provided evidence that IS-associated CpG-SNP rs4073259 may affect the expression level of ALOX5AP through allele-specific methylation and consequently the phenotype of the disease.