THE GENE RNF213 has been significantly associated with vasospastic angina (VSA) and increased likelihood of mortality from acute myocardial infarction, according to recent research. VSA, a potentially life-threatening condition triggered by spontaneous coronary artery spasms, is particularly prevalent in East Asian populations. Researchers aimed to determine the specific genetic factors associated with VSA.
Researchers conducted a genome-wide association study including 5,720 patients with VSA across three datasets, and 153,864 controls without coronary artery disease, using data from the Biobank Japan Project data repository. Genome analysis was carried out using a logistic regression model, accounting for sex, age, smoking status, co-occurrence of type 2 diabetes and other confounding factors.
In the first dataset, significant genetic loci including the RNF213 gene were identified in patients with VSA (odds ratio [OR]: 2.00; p=1.2×10-10), and similarly in the second dataset (OR: 2.71; p=2.7×10-10). An East Asian-specific variant of RNF213, rs112735431, was identified as the lead variant (OR: 2.18; p=2.0×10-18), confirming previous research demonstrating that VSA is particularly prevalent in East Asian populations. In a third, larger dataset (528 patients with VSA and 9900 controls), the analysis further validated the link between RNF213 variants and VSA with an OR of 4.01. The researchers also identified that homozygous carriers of RNF213 were at a greater risk of developing VSA (OR: 18.34; p=7.0×10-6). Additionally, the risk of VSA was found to be greater in males (OR: 2.64) than females (OR: 1.88). Investigation of mortality rates in the cohort revealed that carrying the RNF213 gene was linked to a higher mortality rate from acute myocardial infarction (hazard ratio: 2.71; p=3.3×10-4).
In conclusion, variants of the gene RNF213, especially the East Asian-specific variant rs112735431, are strongly associated with VSA, particularly in males and homozygous carriers, and the presence of this genetic factor is associated with higher rates of mortality from acute myocardial infarction. These findings highlight the need for further research to elucidate the mechanisms underlying the genetic aetiology of VSA.
Katrina Thornber, EMJ
Reference
Hikino K et al. RNF213 variants, vasospastic angina, and risk of fatal myocardial infarction. JAMA Cardiol. 2024;DOI:10.1001/jamacardio.2024.1483.
