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Rare RNF213 variants and the risk of intracranial artery stenosis/occlusion disease in Chinese population: a case-control study

BACKGROUND: RNF213 rare variant-p.R4810K (rs112735431) was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. Considering the allelic heterogeneity, we performed target exome sequencing of RNF213 with the aim to id...

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Autores principales: Liao, Xin, Zhang, Tong, Li, Bingyang, Hu, Shimin, Liu, Junyu, Deng, Jing, Tan, Hongzhuan, Yan, Junxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441181/
https://www.ncbi.nlm.nih.gov/pubmed/30925911
http://dx.doi.org/10.1186/s12881-019-0788-9
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author Liao, Xin
Zhang, Tong
Li, Bingyang
Hu, Shimin
Liu, Junyu
Deng, Jing
Tan, Hongzhuan
Yan, Junxia
author_facet Liao, Xin
Zhang, Tong
Li, Bingyang
Hu, Shimin
Liu, Junyu
Deng, Jing
Tan, Hongzhuan
Yan, Junxia
author_sort Liao, Xin
collection PubMed
description BACKGROUND: RNF213 rare variant-p.R4810K (rs112735431) was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. Considering the allelic heterogeneity, we performed target exome sequencing of RNF213 with the aim to identify the rare variants spectrum and their association with ICASO in a Chinese population and further to explore whether the rare variants carrier patients present specific clinical phenotype. METHODS: Target exome sequencing of RNF213 was performed in 250 ICASO patients using FastTarget sequencing technology. Various filtering process were used to select the candidate variants. Control individuals were obtain from 1000 Genome Project (208 Chinese samples) and GeneSky in-house database (1007 samples). Gene-based association analyses were conducted to identify the association between RNF213 rare variants and ICASO. The clinical characteristics of rare variant carriers and non-carriers were compared using Chi-squared test or Fisher’s exact test. RESULTS: After filtration, 18 rare variants were identified in 39 patients. Gene-based association test showed that rare variants of RNF213 were significantly associated with ICASO (Minor allele frequency < 0.05, WSS p = 4.88 × 10(− 10); SKAT p = 9.68 × 10(− 6); SKAT-O p = 3.42 × 10(− 9)). There were no significant clinical characteristic differences other than the diagnosis age which was older in the carriers than the non-carriers (60.5 ± 6.2 vs 57.3 ± 8.9 years old, p = 0.028). CONCLUSION: Rare variants of RNF213 are associated with ICASO in Chinese. However, there are limited genetic diagnosis values of the gene due to no specific phenotypic presentation in the carriers and non carrier patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-019-0788-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-64411812019-04-11 Rare RNF213 variants and the risk of intracranial artery stenosis/occlusion disease in Chinese population: a case-control study Liao, Xin Zhang, Tong Li, Bingyang Hu, Shimin Liu, Junyu Deng, Jing Tan, Hongzhuan Yan, Junxia BMC Med Genet Research Article BACKGROUND: RNF213 rare variant-p.R4810K (rs112735431) was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. Considering the allelic heterogeneity, we performed target exome sequencing of RNF213 with the aim to identify the rare variants spectrum and their association with ICASO in a Chinese population and further to explore whether the rare variants carrier patients present specific clinical phenotype. METHODS: Target exome sequencing of RNF213 was performed in 250 ICASO patients using FastTarget sequencing technology. Various filtering process were used to select the candidate variants. Control individuals were obtain from 1000 Genome Project (208 Chinese samples) and GeneSky in-house database (1007 samples). Gene-based association analyses were conducted to identify the association between RNF213 rare variants and ICASO. The clinical characteristics of rare variant carriers and non-carriers were compared using Chi-squared test or Fisher’s exact test. RESULTS: After filtration, 18 rare variants were identified in 39 patients. Gene-based association test showed that rare variants of RNF213 were significantly associated with ICASO (Minor allele frequency < 0.05, WSS p = 4.88 × 10(− 10); SKAT p = 9.68 × 10(− 6); SKAT-O p = 3.42 × 10(− 9)). There were no significant clinical characteristic differences other than the diagnosis age which was older in the carriers than the non-carriers (60.5 ± 6.2 vs 57.3 ± 8.9 years old, p = 0.028). CONCLUSION: Rare variants of RNF213 are associated with ICASO in Chinese. However, there are limited genetic diagnosis values of the gene due to no specific phenotypic presentation in the carriers and non carrier patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-019-0788-9) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-29 /pmc/articles/PMC6441181/ /pubmed/30925911 http://dx.doi.org/10.1186/s12881-019-0788-9 Text en © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Liao, Xin
Zhang, Tong
Li, Bingyang
Hu, Shimin
Liu, Junyu
Deng, Jing
Tan, Hongzhuan
Yan, Junxia
Rare RNF213 variants and the risk of intracranial artery stenosis/occlusion disease in Chinese population: a case-control study
title Rare RNF213 variants and the risk of intracranial artery stenosis/occlusion disease in Chinese population: a case-control study
title_full Rare RNF213 variants and the risk of intracranial artery stenosis/occlusion disease in Chinese population: a case-control study
title_fullStr Rare RNF213 variants and the risk of intracranial artery stenosis/occlusion disease in Chinese population: a case-control study
title_full_unstemmed Rare RNF213 variants and the risk of intracranial artery stenosis/occlusion disease in Chinese population: a case-control study
title_short Rare RNF213 variants and the risk of intracranial artery stenosis/occlusion disease in Chinese population: a case-control study
title_sort rare rnf213 variants and the risk of intracranial artery stenosis/occlusion disease in chinese population: a case-control study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441181/
https://www.ncbi.nlm.nih.gov/pubmed/30925911
http://dx.doi.org/10.1186/s12881-019-0788-9
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