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.

Retracted Article: Long noncoding RNA ANRIL protects cardiomyocytes against hypoxia/reoxygenation injury by sponging miR-195-5p and upregulating Bcl-2

“…[32][33][34] Additionally, the variants on ANRIL promoter and exons associated with ANRIL expression contribute to the risk of myocardial infarction. 35 In the present study, our data supported that ANRIL was downregulated in the serum of AMI patients, consistent with a previous work. 6 Moreover, we veried that H/R treatment time-dependently decreased ANRIL expression in myocardial cells.…”

Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review

“…More recently, a consistent association between two variants in the 9p21.3 locus (rs10965215 and rs10738605) and CAD has been reported also in the Chinese Han population (Cheng et al, 2017 ). For rs10965215, unconditional logistic regression analysis revealed that the G allele increased MI risk with OR of 1.37 (95% CI = 1.05–1.78, P = 0.020).…”

“…For rs10965215, unconditional logistic regression analysis revealed that the G allele increased MI risk with OR of 1.37 (95% CI = 1.05–1.78, P = 0.020). For rs10738605, C allele conferred increased MI risk with OR of 1.38 (95% CI = 1.06–1.80, P = 0.019) as compared to the G allele after adjustment for conventional risk factors (Cheng et al, 2017 ).…”

9P21.3 locus; An Important Region in Coronary Artery Disease: A Panel Approach to Investigation of the Coronary Artery Disease Etiology

“…The majority of SNP in the ANRIL gene were located in intronic regions, but recently two exonic variants were reported to be associated with MI. Sequencing of the promoter region and UTR upstream of ANRIL showed no variant significantly associated with MI [138]. Some other studies investigating the effects of 9p21.3 variants on expression and regulation of 9p21.3 genes indicated that rs1333049 altered the expression of CDKN2A/B and ANRIL.…”