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. 2017 Feb 21;8(8):12607-12619.
doi: 10.18632/oncotarget.14721.

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

Jie Cheng  1   2 , Meng-Yun Cai  1   3 , Yu-Ning Chen  1   3 , Zhi-Cheng Li  1   3 , Sai-Sai Tang  1   3 , Xi-Li Yang  4 , Can Chen  5 , Xinguang Liu  1   3   6 , Xing-Dong Xiong  1   3   6
Affiliations

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

Jie Cheng et al. Oncotarget. .

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.

Keywords: ANRIL; Gerotarget; myocardial infarction; risk; single nucleotide polymorphism.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1. Pairwise linkage disequilibrium between ANRIL variants
ANRIL gene is composed of 20 exons which are represented as boxes. D’ values are plotted as a graph to show linkage disequilibrium between these variants. The schematic of primer binding sites for EU741058.1 was shown at the top. Arrows represented forward and reverse primers and the reverse primer spanning exons 7 to 20.
Figure 2
Figure 2. Prediction of the secondary structure of ANRIL by Mfold
dG, the predicted folding energy. The polymorphism site was indicated by red arrow. The RNA with rs10965215 A allele required lower free energy for folding (dG) compared with the one with rs10965215 G allele (A. and B.) at 37˚C. The RNA with rs10738605 G allele required lower dG compared with the one with rs10738605 C allele (C. and D.)
Figure 3
Figure 3. Relationship of ANRIL transcript EU741058.1 with rs10965215 and rs10738605 in PBMCs in the sum of MI patients and control subjects
Analysis of ANRIL transcript EU741058.1 expression levels in PBMCs of individuals carrying GG/AG genotypes vs. AA genotype for rs10965215 (A.) Analysis of ANRIL transcript EU741058.1 expression levels in PBMCs of individuals carrying CC/CG genotypes vs. CC genotype for rs10738605 (B.)
See this image and copyright information in PMC

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