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Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms

Intracranial aneurysms (IAs) accounts for 85% of hemorrhagic stroke. Genetic factors have been known to play an important role in the development of IAs. A functional CNV (CNV-67048) of human WW domain-containing oxidoreductase (WWOX), which has been identified as a tumor suppressor gene in multiple...

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Autores principales: Fan, Jin, Sun, Wen, Lin, Min, Yu, Ke, Wang, Jian, Duan, Dan, Zheng, Bo, Yang, Zhenghui, Wang, Qingsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941300/
https://www.ncbi.nlm.nih.gov/pubmed/26910372
http://dx.doi.org/10.18632/oncotarget.7546
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author Fan, Jin
Sun, Wen
Lin, Min
Yu, Ke
Wang, Jian
Duan, Dan
Zheng, Bo
Yang, Zhenghui
Wang, Qingsong
author_facet Fan, Jin
Sun, Wen
Lin, Min
Yu, Ke
Wang, Jian
Duan, Dan
Zheng, Bo
Yang, Zhenghui
Wang, Qingsong
author_sort Fan, Jin
collection PubMed
description Intracranial aneurysms (IAs) accounts for 85% of hemorrhagic stroke. Genetic factors have been known to play an important role in the development of IAs. A functional CNV (CNV-67048) of human WW domain-containing oxidoreductase (WWOX), which has been identified as a tumor suppressor gene in multiple cancers, was identified to be associated with gliomas risk previously. Here, we hypothesized that the CNV-67048 could also affect susceptibility of IAs. Based on a two-stage, case(−) control study with a total of 976 patients of IAs and 1,200 matched healthy controls, we found the effect size for per copy deletion was 1.35 (95% CI = 1.16–1.57; P(trend) = 1.18 × 10(−4)). Compared with the individuals having no deletion, significantly higher risk of IAs was detected for both subjects carrying 1 copy deletion (OR = 1.24, 95% CI = 1.02–1.52) and subjects carrying 2 copy deletion (OR = 1.77, 95% CI = 1.24–2.53). Real-time PCR was used to confirm the abnormal expression of WWOX in tissues of IA patients and influence of genotypes of CNV-67048. The expression level of WWOX in IA tissues was significantly lower than that in corresponding normal tissues (P = 0.004), and the deletion genotypes of CNV-67048 have lower WWOX mRNA levels in both tumor tissues and border tissues (P < 0.01). Our data suggests that the deletion genotypes of CNV-67048 in WWOX predispose their carriers to IAs, which might be a genetic biomarker to predict risk of IAs in Chinese.
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spelling pubmed-49413002016-07-19 Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms Fan, Jin Sun, Wen Lin, Min Yu, Ke Wang, Jian Duan, Dan Zheng, Bo Yang, Zhenghui Wang, Qingsong Oncotarget Research Paper Intracranial aneurysms (IAs) accounts for 85% of hemorrhagic stroke. Genetic factors have been known to play an important role in the development of IAs. A functional CNV (CNV-67048) of human WW domain-containing oxidoreductase (WWOX), which has been identified as a tumor suppressor gene in multiple cancers, was identified to be associated with gliomas risk previously. Here, we hypothesized that the CNV-67048 could also affect susceptibility of IAs. Based on a two-stage, case(−) control study with a total of 976 patients of IAs and 1,200 matched healthy controls, we found the effect size for per copy deletion was 1.35 (95% CI = 1.16–1.57; P(trend) = 1.18 × 10(−4)). Compared with the individuals having no deletion, significantly higher risk of IAs was detected for both subjects carrying 1 copy deletion (OR = 1.24, 95% CI = 1.02–1.52) and subjects carrying 2 copy deletion (OR = 1.77, 95% CI = 1.24–2.53). Real-time PCR was used to confirm the abnormal expression of WWOX in tissues of IA patients and influence of genotypes of CNV-67048. The expression level of WWOX in IA tissues was significantly lower than that in corresponding normal tissues (P = 0.004), and the deletion genotypes of CNV-67048 have lower WWOX mRNA levels in both tumor tissues and border tissues (P < 0.01). Our data suggests that the deletion genotypes of CNV-67048 in WWOX predispose their carriers to IAs, which might be a genetic biomarker to predict risk of IAs in Chinese. Impact Journals LLC 2016-02-21 /pmc/articles/PMC4941300/ /pubmed/26910372 http://dx.doi.org/10.18632/oncotarget.7546 Text en Copyright: © 2016 Fan et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Fan, Jin
Sun, Wen
Lin, Min
Yu, Ke
Wang, Jian
Duan, Dan
Zheng, Bo
Yang, Zhenghui
Wang, Qingsong
Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms
title Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms
title_full Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms
title_fullStr Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms
title_full_unstemmed Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms
title_short Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms
title_sort genetic association study identifies a functional cnv in the wwox gene contributes to the risk of intracranial aneurysms
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941300/
https://www.ncbi.nlm.nih.gov/pubmed/26910372
http://dx.doi.org/10.18632/oncotarget.7546
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