title: Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms.
abstract: 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; Ptrend = 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.
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Neurology, Jinling Hospital of Nanjing University, Nanjing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Neurology, Fuzhou General Hospital of Nanjing Command, PLA and Clinical Medical College of Fujian Medical University, Fuzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Duan
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurology, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
keywords: SNP; WWOX; gene; intracranial aneurysm; risk factor