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Variants in ANRIL gene correlated with its expression contribute to myocardial infarction risk.

ABSTRACT: ANRIL (antisense non-coding RNA in the INK4 locus), located at the 9p21.3 locus, has been known to be closely associated with the risk of coronary artery disease (CAD). To date, studies of the 9p21.3 variants on CAD risk mainly focus on the non-coding region of ANRIL. However, the biological significance of the variants on ANRIL promoter and exons is still unknown. Here we investigate whether the variants on ANRIL promoter and exons have an effect on myocardial infarction (MI) risk, and further analyze the association of these variants with the expression of ANRIL transcript. We did not find any common variants with minor allele frequencies (MAF) larger than 5% in ANRIL promoter by sequencing 1.6kb upstream of the start codon. Unconditional logistic regression analysis revealed that two SNPs in ANRIL exons, rs10965215 and rs10738605, were significantly associated with MI risk. Further studies revealed that ANRIL transcript EU741058.1 expression levels of rs10965215 and rs10738605 risk genotypes were borderline lower than those of protective genotypes. Our data provide the evidence that the variants rs10965215 and rs10738605 in ANRIL exons contribute to MI risk in the Chinese Han population which might be correlated with the expression of its transcript EU741058.1.

SUBMITTER: Cheng J

PROVIDER: S-EPMC5355039 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Variants in ANRIL gene correlated with its expression contribute to myocardial infarction risk.

Cheng Jie J Cai Meng-Yun MY Chen Yu-Ning YN Li Zhi-Cheng ZC Tang Sai-Sai SS Yang Xi-Li XL Chen Can C Liu Xinguang X Xiong Xing-Dong XD

Oncotarget 20170201 8

ANRIL (antisense non-coding RNA in the INK4 locus), located at the 9p21.3 locus, has been known to be closely associated with the risk of coronary artery disease (CAD). To date, studies of the 9p21.3 variants on CAD risk mainly focus on the non-coding region of ANRIL. However, the biological significance of the variants on ANRIL promoter and exons is still unknown. Here we investigate whether the variants on ANRIL promoter and exons have an effect on myocardial infarction (MI) risk, and further ...[more]

PMID: 28107200

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Project description:BackgroundGenetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.MethodsPeripheral blood samples from 338 subjects aged 62 ± 11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N = 175, and replication N = 163), and followed for a mean 2.4 years for cardiovascular death. Gene expression was measured on Illumina HT-12 microarrays with two different normalization procedures to control technical and biological covariates. Whole genome genotyping was used to support comparative genome-wide association studies of gene expression. Analysis of variance was combined with receiver operating curve and survival analysis to define a transcriptional signature of cardiovascular death.ResultsIn both phases, there was significant differential expression between healthy and AMI groups with overall down-regulation of genes involved in T-lymphocyte signaling and up-regulation of inflammatory genes. Expression quantitative trait loci analysis provided evidence for altered local genetic regulation of transcript abundance in AMI samples. On follow-up there were 31 cardiovascular deaths. A principal component (PC1) score capturing covariance of 238 genes that were differentially expressed between deceased and survivors in the discovery phase significantly predicted risk of cardiovascular death in the replication and combined samples (hazard ratio = 8.5, P < 0.0001) and improved the C-statistic (area under the curve 0.82 to 0.91, P = 0.03) after adjustment for traditional covariates.ConclusionsA specific blood gene expression profile is associated with a significant risk of death in Caucasian subjects with CAD. This comprises a subset of transcripts that are also altered in expression during acute myocardial infarction.

Dataset Information

Variants in ANRIL gene correlated with its expression contribute to myocardial infarction risk.

Publications

Variants in ANRIL gene correlated with its expression contribute to myocardial infarction risk.

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