title: A Potential Polymorphism in the Promoter of Let-7 is Associated With an Increased Risk of Intracranial Aneurysm: A Case-Control Study.
abstract: Let-7 family plays a key role in the progression of atherosclerosis and intracranial aneurysm (IA). We hypothesized that rs10877887 and rs13293512 polymorphisms in the promoters of let-7 family may be associated with the susceptibility of IA. We genotyped the 2 single nucleotide polymorphisms (SNPs) in 305 patients with IA and 401 healthy controls. The rs10877887 was analyzed using a polymerase chain reaction-restriction fragment length polymorphism assay, and the rs13293512 was analyzed using a TaqMan SNP genotyping method. The relative expression of let-7 family was measured in plasma of cases and controls using real-time PCR. We found that the rs13293512CT genotype was associated with a significantly increased risk of developing IA in a heterozygote comparison (adjusted OR = 1.43, 95% CI, 1.00-2.05, P = 0.048) and dominant comparison (adjusted OR = 1.44, 95% CI, 1.02-2.03, P = 0.04). Combined analysis showed that the rs10877887TT and rs13293512CC/CT genotypes had a significantly increased risk of IA (OR = 1.67, 95% CI, 1.04-2.68, P = 0.03). Moreover, the levels of let-7a, let-7d, and let-7f were downregulated in IA patients, and patients with the rs13293512CC/CT genotypes had a lower level of let-7a than those with rs13293512TT genotype (P = 0.03). These findings indicate that the rs13293512CC/CT is a risk factor for the development of IA, possibly because of the genotypes resulting in a lower level of let-7a.
authors.affiliation: From the Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, P. R. China.
authors.forename: Xiutian
authors.initials: X
authors.lastname: Sima
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Peizhi
authors.initials: P
authors.lastname: Zhou
authors.forename: Chao
authors.initials: C
authors.lastname: You
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: D035683:MicroRNAs; C487931:mirnlet7 microRNA, human