Differential Effects of Chromosome 9p21 Variation on Subphenotypes of Intracranial Aneurysm Site Distribution
Differential Effects of Chromosome 9p21 Variation on Subphenotypes of Intracranial Aneurysm Site Distribution
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DOI：
10.1161/strokeaha.110.586529
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发表时间：
2010-08-01
期刊：
影响因子：
8.3
通讯作者：
Inoue, Ituro
中科院分区：
文献类型：
--
作者：
Nakaoka, Hirofumi;Takahashi, Tomoko;Inoue, Ituro
背景和目的：最近，一项全基因组关联研究确定了染色体9 p21单核苷酸多态性与颅内动脉瘤（IA）风险之间的关联。动脉瘤特征或颅内动脉瘤的亚表型，如蛛网膜下腔出血史、存在多个颅内动脉瘤和颅内动脉瘤的位置，具有临床重要性。我们调查是否9 p21变异和IA的风险之间的关联变化，这些subphenotypes. Methods，我们进行了一项病例对照研究，981例和699例控制在日本。标记9 p21风险位点的4个单核苷酸多态性进行基因分型。结果在4种单核苷酸多态性中，rs 1333040与IA的关联性最强（P = 1.5 × 10 - 6;每个等位基因的OR为1.43; 95% CI为1.24-1.66）。没有患者特征（性别、年龄、吸烟和高血压）是该关联的显著混杂因素或效应修饰因素。IA亚表型的亚组分析显示，在最常见的IA部位中，与后交通动脉IA的相关性最强（OR，1.69; 95% CI，1.26-2.26），与前交通动脉IA的相关性不显著（OR，1.22; 95% CI，0.96-1.57）。当对IA部位进行二分时，后循环-后交通动脉组（OR，1.73; 95% CI，1.32-2.26）与前循环组（OR，1.28; 95% CI，1.07-1.53）的IA相关性更强。这些OR的异质性显著（P=0.032）。当按蛛网膜下腔出血史分层时，这些关联没有变化（破裂IA的OR，1.42; 95% CI，1.18-1.71;未破裂IA的OR，1.27; 95% CI，1.00-1.62）或IA多重性（OR，1.57; 95%CI，1.21-2.03对于多个IA; OR，1.36; 95%CI，1.15-1.61对于单个IA）。（中风。2010; 41：1593-1598）。
Background and Purpose-Recently, a genome-wide association study identified associations between single nucleotide polymorphisms on chromosome 9p21 and risk of harboring intracranial aneurysm (IA). Aneurysm characteristics or subphenotypes of IAs, such as history of subarachnoid hemorrhage, presence of multiple IAs and location of IAs, are clinically important. We investigated whether the association between 9p21 variation and risk of IA varied among these subphenotypes.Methods-We conducted a case-control study of 981 cases and 699 controls in Japanese. Four single nucleotide polymorphisms tagging the 9p21 risk locus were genotyped. The OR and 95% CI were estimated using logistic regression analyses.Results-Among the 4 single nucleotide polymorphisms, rs1333040 showed the strongest evidence of association with IA (P = 1.5 x 10(-6); per allele OR, 1.43; 95% CI, 1.24-1.66). None of the patient characteristics (gender, age, smoking, and hypertension) was a significant confounder or effect modifier of the association. Subgroup analyses of IA subphenotypes showed that among the most common sites of IAs, the association was strongest for IAs of the posterior communicating artery (OR, 1.69; 95% CI, 1.26-2.26) and not significant for IAs in the anterior communicating artery (OR, 1.22; 95% CI, 0.96-1.57). When dichotomizing IA sites, the association was stronger for IAs of the posterior circulation-posterior communicating artery group (OR, 1.73; 95% CI, 1.32-2.26) vs the anterior circulation group (OR, 1.28; 95% CI, 1.07-1.53). Heterogeneity in these ORs was significant (P=0.032). The associations did not vary when stratifying by history of subarachnoid hemorrhage (OR, 1.42; 95% CI, 1.18-1.71 for ruptured IA; OR, 1.27; 95% CI, 1.00-1.62 for unruptured IA) or by multiplicity of IA (OR, 1.57; 95% CI, 1.21-2.03 for multiple IAs; OR, 1.36; 95% CI, 1.15-1.61 for single IA).Conclusions-Our results suggest that genetic influence on formation may vary between IA subphenotypes. (Stroke. 2010; 41: 1593-1598.)