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RNF213 polymorphism and Moyamoya disease: A systematic review and meta-analysis
1Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.
Background:
Recent genome-wide and locus-specific association studies identified RNF213 as an important Moyamoya disease (MMD) susceptibility gene. But the results of these studies are limited by the few subjects, different methodologies and ethnicities.
Aims:
To investigate the association between p.R4810K (rs 112735431, ss179362673; G > A) and p.R4859K (c.14576 G > A) polymorphisms of the RNF213 gene and MMD susceptibility.
Settings And Design:
We conducted a meta-analysis to evaluate the association.
Materials And Methods:
Two investigators independently searched the PubMed, Medline, and Embase databases for studies published before October 2012. For included studies, we performed meta-analyses using Cochrane RevMan software.
Statistical Analysis:
Summary odds ratios (ORs) and 95% confidence intervals (CIs) for RNF213 p.R4810K and p.R4859K polymorphisms; MMD were calculated in a fixed-effects model and a random effects model whenever appropriate.
Results:
Five eligible studies were reviewed and analyzed, which included two studies for p.R4810K polymorphisms (421 cases and 1214 controls) and three studies for p.R4859K polymorphisms (398 cases and 765 controls). Overall, the pooled results indicated that both p.R4810K polymorphisms and p.R4859K polymorphisms were associated with MMD risk (OR 92.03, 95% CI 54.06-156.65, P < 0.00001 and OR 157.53, 95% CI 85.37-290.7, P < 0.00001, respectively). Stratified analyses by ethnicity revealed the population attributable risks in the Japanese and Korean populations were larger than that in the Chinese population (P =0.0006).
Conclusions:
This meta-analysis demonstrated that there are strong associations between p.R4859K and p.R4810K polymorphisms of the RNF213 gene and MMD. The discoveries of its association with MMD may help in early diagnosis and prevention of this disease. Further study is still necessary to clarify the biochemical function and pathological role of RNF213 in MMD.
Insights
This meta-analysis confirms strong associations between RNF213 gene polymorphisms (p.R4810K and p.R4859K) and Moyamoya disease (MMD) susceptibility. These findings may aid in early MMD diagnosis and prevention strategies.
Area of Science:
- Genetics
- Neurology
- Epidemiology
Background:
- Recent studies highlight RNF213 as a key Moyamoya disease (MMD) susceptibility gene.
- Previous research was limited by small sample sizes, diverse methodologies, and varying ethnicities.
Purpose of the Study:
- To investigate the association between RNF213 gene polymorphisms (p.R4810K and p.R4859K) and MMD susceptibility using a meta-analysis.
- To consolidate evidence from multiple studies to provide a more robust assessment of the genetic risk.
Main Methods:
- A comprehensive meta-analysis was conducted, searching PubMed, Medline, and Embase databases for relevant studies published before October 2012.
- Data from five eligible studies, including analyses of p.R4810K (421 cases, 1214 controls) and p.R4859K (398 cases, 765 controls) polymorphisms, were pooled using Cochrane RevMan software.
- Fixed-effects and random-effects models were employed to calculate summary odds ratios (ORs) and 95% confidence intervals (CIs).
Main Results:
- The meta-analysis revealed significant associations between both RNF213 p.R4810K and p.R4859K polymorphisms and MMD risk.
- Pooled results indicated strong associations: OR 92.03 (95% CI 54.06-156.65, P < 0.00001) for p.R4810K and OR 157.53 (95% CI 85.37-290.7, P < 0.00001) for p.R4859K.
- Stratified analyses by ethnicity showed higher population attributable risks in Japanese and Korean populations compared to the Chinese population (P = 0.0006).
Conclusions:
- This meta-analysis strongly supports the association between RNF213 p.R4859K and p.R4810K polymorphisms and Moyamoya disease.
- These genetic findings offer potential for improving early diagnosis and prevention strategies for MMD.
- Further research is warranted to elucidate the precise biochemical functions and pathological roles of RNF213 in MMD pathogenesis.
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