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Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease
Takaaki Morimoto1,2, Yohei Mineharu1, Koh Ono3
1Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Insights
The RNF213 p.R4810K variant is linked to coronary artery disease in Japanese individuals. This finding may help understand genetic risk factors for heart disease in Asian populations.
Area of Science:
- Genetics
- Cardiovascular Science
- Neurology
Background:
- The genetic basis of coronary artery disease (CAD) remains incompletely understood, particularly in Asian populations.
- Moyamoya disease, a progressive cerebrovascular condition, is sometimes associated with CAD.
- The RNF213 p.R4810K variant is prevalent in Japanese Moyamoya disease patients, suggesting its potential role in CAD.
Purpose of the Study:
- To investigate the association between the RNF213 p.R4810K variant and coronary artery disease in the Japanese population.
- To determine if RNF213 p.R4810K is a risk factor for CAD.
Main Methods:
- Genotyping of the RNF213 p.R4810K variant in 956 CAD patients and 716 controls.
- Replication analysis in an independent cohort (311 CAD patients, 494 controls).
- Multivariate logistic regression analysis, adjusting for known risk factors like dyslipidemia and smoking.
Main Results:
- The RNF213 p.R4810K minor allele frequency was significantly higher in CAD patients (2.04%) versus controls (0.98%) in the primary study (OR=2.11, p=0.017).
- After adjusting for risk factors, the association remained significant under a dominant model (OR=2.90, p=0.005).
- The replication study showed a significant association after adjusting for age and sex (OR=4.99, p=0.031), but not when further adjusted for risk factors (OR=3.82, p=0.076).
Conclusions:
- The RNF213 p.R4810K variant shows a significant association with coronary artery disease in the Japanese population.
- This variant may represent a genetic risk factor for CAD in this demographic.
Background:
The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested.
Methods And Results:
We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87-16.77; p = 0.076).
Conclusions:
The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.