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.

Effectiveness of thymectomy in juvenile myasthenia gravis and clinical characteristics associated with better outcomes.

Thymectomy is an established treatment in adult myasthenia gravis, but its exact role in juvenile myasthenia gravis (JMG) is still uncertain. Thymectomy is frequently considered in the treatment of severe, medically refractory JMG. Surgical approaches have evolved from open median sternotomy to the more cosmesis-preserving thoracoscopic approach. This paper reviews current evidence on the effectiveness of thymectomy in JMG and discusses clinical characteristics which may be associated with improved outcomes. 17 studies including 588 patients who underwent thymectomy from 1997 to 2020 were found, which either reported uncontrolled cohorts undergoing thymectomy, or compared cohorts undergoing different surgical approaches. An improvement in clinical status or reduced requirement for medical therapy following thymectomy was seen in 453 patients (77%). Complete remission was seen in 40% (n = 172/430). Thoracoscopic approaches may provide improved outcomes, fewer complications, and better cosmetic outcomes. Better surgical outcomes may be associated with early intervention, intervention after the onset of puberty, being acetylcholine receptor antibody positive, having more severe disease and the presence of hyperplastic thymic tissue. However, analysis remains hindered by the limitations of the currently available retrospective studies of small cohorts. Nonetheless, available literature suggests a role for thymectomy in JMG patients, especially those with certain clinical characteristics.