The Association of ANRIL With Coronary Artery Disease And Aortic Aneurysms, How Far Does The Gene Desert Go?

BACKGROUND

Coronary artery disease (CAD) and aortic aneurysms (AA) are 2 cardiovascular diseases that share a multifactorial aetiology. The influence of family history and genetics on the 2 diseases separately and in association is well known, but poorly elucidated. This comprehensive review aims to examine the current literature on the gene ANRIL (antisense non-coding RNA in the INK4 locus) and its associations with CAD and AA.

METHODS

A database search on OVID, PubMed and Cochrane to identify articles concerning single nucleotide polymorphisms (SNPs) associated with ANRIL and their respective incidences of, and impact on, CAD and AA across populations.

RESULTS

Cohort studies across various ethnicities reveal that various ANRIL SNPs are significantly associated separately with CAD (rs1333040, rs1333049 and rs2383207) and AA (rs564398, rs10757278 and rs1333049), and that these SNPs are present in significant proportions of the population. SNP rs1333049 is significantly associated with both diseases, but is positively correlated with AAA and negatively correlated with CAD. This review further outlines several pathophysiological links via endothelial and adventitial cells, vascular smooth muscle cells and sense gene interaction, which may explain these genetic associations identified.

CONCLUSION

Given the associations uncovered between ANRIL polymorphisms and CAD and AA, as well as the molecular mechanisms which may explain the underlying pathophysiology, ANRIL appears to be strongly linked with both diseases. ANRIL may hence have a future application in screening normal patients and risk stratifying patients with both diseases. Its role in linking the 2 diseases is yet unclear, warranting further studies.