title: A functional variant of the collagen type III alpha1 gene modify risk of sporadic intracranial aneurysms.
abstract: Abnormalities in type III collagen in the arterial walls cause certain familial intracranial aneurysms (IAs); however, it remains unknown whether COL3A1 variants contribute to the risk of sporadic IAs. To study whether COL3A1 variants are associated with sporadic IAs, the association of COL3A1 variants with sporadic IAs was tested in 298 cases and 488 controls, replicated in an independent population of 192 cases and 1,690 controls, and further verified in 633 patients with intra-cerebral hemorrhage, 1,074 hypertensives, and 1,883 controls. We found that allele A of SNP rs1800255 conferred a 1.71-fold increased risk for IAs (adjusted odds ratio: OR = 1.71, 95% confidence interval: CI 1.19-2.45, P = 0.004) and results in an amino acid change of Ala698Thr, which led to a lower thermal stability of the peptide. These results were confirmed in the independent study. The associations were independent of the presence of hemorrhagic stroke and hypertension. These results support the view that the functional variant of COL3A1 is genetic risk factors for IAs in the Chinese population.
authors.affiliation: Sino-German Laboratory for Molecular Medicine, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishilu, Beijing 100037, People's Republic of China.
authors.forename: Jingzhou
authors.initials: J
authors.lastname: Chen
authors.forename: Yufang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Jiang
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Weihua
authors.initials: W
authors.lastname: Song
authors.forename: Liming
authors.initials: L
authors.lastname: Luan
authors.forename: Kejia
authors.initials: K
authors.lastname: Lou
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.forename: Qi
authors.initials: Q
authors.lastname: Pang
authors.forename: Rutai
authors.initials: R
authors.lastname: Hui
mesh_terms: D000483:Alleles; D002681:China / Q000453:epidemiology; D024061:Collagen Type III / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D002532:Intracranial Aneurysm / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C439971:COL3A1 protein, human; D024061:Collagen Type III