title: Association between functional polymorphisms in the promoter of the miR-143/145 cluster and risk of intracranial aneurysm.
abstract: MicroRNAs (miRs)-143/145 are involved in various biological processes related to aneurysm formation and are downregulated in patients with intracranial aneurysm (IA). We aimed to determine whether two functional polymorphisms (i.e. rs4705342 and rs4705343) in the promoter of miR-143/145 are related to IA risk. A case-control study was undertaken to examine the association of rs4705342 and rs4705343 with IA risk, including 565 patients with IA and 622 age- and gender-matched controls. rs4705342 was analysed by TaqMan Assay, and rs4705343 was genotyped using polymerase chain reaction-restriction fragment length polymorphism. miR-143/145 expression was quantified using RT-PCR. rs4705342 was associated with a significantly lower risk of IA, with adjusted ORs of 0.74 (95% CI: 0.58-0.95) for TC genotype carriers and 0.74 (95% CI: 0.59-0.94) for TC/CC genotypes carriers. Individuals carrying the rs4705342 C allele had a reduced risk of IA (adjusted OR = 0.82; 95% CI: 0.68-0.98). Haplotype of the two loci of rs4705342 and rs4705343 showed that the CT haplotype carried a lower IA risk and higher miR-143 level. Moreover, the rs4705342 CC/CT genotypes were associated with higher miR-143 levels. Thus, the rs4705342C-rs4705343T haplotype in the promoter of miR-143/145 cluster may be related to IA development.
authors.affiliation: Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
authors.forename: Xiutian
authors.initials: X
authors.lastname: Sima
authors.affiliation: Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
authors.forename: Peizhi
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: You
authors.affiliation: Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Cai
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D002532:Intracranial Aneurysm / Q000097:blood / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D005810:Multigene Family; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018570:Risk Assessment
chemical_list: C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs