Association of polymorphisms in long non-coding RNA H19 with coronary artery disease risk in a Chinese population

Abstract

H19 is an imprinted gene transcribing a long non-coding RNA and is downregulated postnatally. Re-expression of H19 has been observed in patients with atherosclerosis. However, to date, no data has been published on the association of H19 polymorphisms with the risk of coronary artery disease (CAD). In this study, four polymorphisms, rs217727, rs2067051, rs2251375, rs4929984, were analyzed in 701 CAD patients and 873 age- and sex-matched control subjects. Polymorphisms were genotyped by TaqMan technology. Our data showed that the T variant of rs217727 was associated with an increased risk of CAD [additive model: odds ratio (OR)=2.05, 95%CI=1.35-3.12; dominant model: OR=1.46, 95% confidence interval (CI)=1.12-1.90; recessive model: OR=1.75, 95%CI=1.18-2.58], while A variant of rs2067051 was associated with a decreased risk of CAD (additive model: OR=0.66, 95%CI=0.45-0.96; recessive model: OR=0.71, 95%CI=0.50-0.99). Combined analysis showed that subjects carrying 3 or 4 risk alleles had a significantly increased risk of CAD, relative to those with 0-2 risk alleles (OR=1.61, 95%CI=1.20-2.15). Moreover, CAD patients with 3 or 4 risk alleles also had significantly higher Gensini scores than those with 0-2 risk alleles (P=0.001). Further haplotype-based analysis revealed that individuals with C-G-C-C, T-G-A-A, and T-A-A-A haplotypes indicated a higher prevalence of CAD (OR=1.88, 95%CI=1.03-3.43; OR=2.26, 95%CI=1.19-4.31; OR=2.66, 95%CI=1.34-5.25, respectively), compared to individuals with the most common C-G-A-C haplotype. In conclusion, our study demonstrates for the first time that common polymorphisms of H19 are associated with the risk and severity of CAD in a Chinese population. Future studies are needed to explore the underlying mechanisms of our findings.

Keywords: Coronary artery disease; H19; Long non-coding RNA; Polymorphism.