Sima Xiutian, Sun Hong, Zhou Peizhi, You Chao
From the Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan, P. R. China.
Medicine (Baltimore). 2015 Dec;94(51):e2267. doi: 10.1097/MD.0000000000002267.
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.
Let-7家族在动脉粥样硬化和颅内动脉瘤（IA）的进展中起关键作用。我们假设Let-7家族启动子中的rs10877887和rs13293512多态性可能与IA的易感性相关。我们对305例IA患者和401例健康对照者的这两个单核苷酸多态性（SNP）进行了基因分型。rs10877887采用聚合酶链反应-限制性片段长度多态性分析，rs13293512采用TaqMan SNP基因分型方法进行分析。使用实时PCR检测病例组和对照组血浆中Let-7家族的相对表达。我们发现，在杂合子比较中（校正OR = 1.43，95%CI，1.00 - 2.05，P = 0.048）和显性比较中（校正OR = 1.44，95%CI，1.02 - 2.03，P = 0.04），rs13293512 CT基因型与IA发生风险显著增加相关。联合分析显示，rs10877887 TT和rs13293512 CC/CT基因型患IA的风险显著增加（OR = 1.67，95%CI，1.04 - 2.68，P = 0.03）。此外，IA患者中Let-7a、Let-7d和Let-7f水平下调，rs13293512 CC/CT基因型患者的Let-7a水平低于rs13293512 TT基因型患者（P = 0.03）。这些发现表明，rs13293512 CC/CT是IA发生的一个危险因素，可能是因为这些基因型导致Let-7a水平降低。
