Introduction: Intracranial major artery stenosis/occlusion (ICASO) is a common cause of ischemic stroke worldwide. A number of studies have assessed the association of the p.R4810K polymorphism in the ring finger protein 213 (RNF213) gene with ICASO, but the results have not been entirely consistent.
Methods: We conducted a case-control study to estimate the association between the p.R4810K polymorphism and the risk of ICASO in a Chinese population. A total of 124 patients and 230 controls were enrolled. Moreover, a meta-analysis was performed to evaluate this association in the East Asian populations.
Results: In our case control study, the frequencies of the G/A genotype of p.R4810K were significantly higher in the ICASO patients than in the control group (4.03% vs. 0.43%, P=0.021, respectively). Moreover, in the meta-analysis, we assessed 7 case-control studies that included 1239 patients and 1377 controls. The pooled odds ratios (ORs) indicated significant association between the p.R4810K polymorphism and the ICASO risk in the dominant model (OR=9.37, 95% confidence interval, CI: 4.61-19.02, P=0.000), the heterozygote comparison (OR=8.97, 95% CI: 4.41-18.25, P=0.000) and the allele comparison (OR=9.50, 95% CI: 4.71-19.19, P=0.000) in the East Asian populations. Subgroup analysis based on ethnicity revealed that the risks in the Japanese and Korean populations were larger than that in the Chinese population.
Conclusions: The p.R4810K polymorphism was associated with an increased risk of ICASO in the East Asian populations. Further studies on the function of the RNF213 protein and the clinical features of this subtype of ICASO are needed.
Patient Care: Intracranial major artery stenosis/occlusion (ICASO) is one of the most common causes of ischemic stroke worldwide. ICASO is known to be common among nonwhite populations, particularly Asian populations, which indicates the potential involvement of genetic factors. However, genetic polymorphisms that are specifically related to ICASO have not been elucidated to date. Recently, the ring finger protein 213 (RNF213) gene p.R4810K polymorphism was found to be significantly associated with the risk of ICASO in small studies in Japanese and Korea populations. We conducted a case–control study to evaluate this association in a Chinese population. Furthermore, we conducted a meta-analysis to evaluate this association in East Asians. Our study indicated that the p.R4810K polymorphism is associated with ICASO in Chinese population. Moreover, in the meta-analysis, we assessed 7 case-control studies, including 1239 patients and 1377 controls. Pooled odds ratios (ORs) indicated a significant association between the p.R4810K polymorphism and ICASO risk in the dominant model (OR=9.37, 95%CI: 4.61-19.02, P=0.000), the heterozygote comparison (OR=8.97, 95% CI: 4.41-18.25, P=0.000) and the allele comparison (OR=9.50, 95% CI: 4.71-19.19, P=0.000) in East Asian populations. Subgroup analysis based on ethnicity revealed the population attributable risks in the Japanese and Korean populations were larger than that in the Chinese population. The results enhance our understanding of the genetic background of ICASO. Screening for the p.R4810K variant in ICASO patients in Asia is important to prevent future strokes and comorbidities.
Learning Objectives: The p.R4810K polymorphism is associated with ICASO in East Asian populations.
The results enhance our understanding of the genetic background of ICASO.