Kaushal Ritesh, Woo Daniel, Pal Prodipto, Haverbusch Mary, Xi Huifeng, Moomaw Charles, Sekar Padmini, Kissela Brett, Kleindorfer Dawn, Flaherty Matthew, Sauerbeck Laura, Chakraborty Ranajit, Broderick Joseph, Deka Ranjan
Department of Environmental Health, Center for Genome Information, University of Cincinnati, Cincinnati, Ohio, USA.
BMC Med Genet. 2007 Jul 31;8:49. doi: 10.1186/1471-2350-8-49.
Apolipoprotein E (APOE) and elastin (ELN) are plausible candidate genes involved in the pathogenesis of stroke. We tested for association of variants in APOE and ELN with subarachnoid hemorrhage (SAH) in a population-based study. We genotyped 12 single nucleotide polymorphisms (SNPs) on APOE and 10 SNPs on ELN in a sample of 309 Caucasian individuals, of whom 107 are SAH cases and 202 are age-, race-, and gender-matched controls from the Greater Cincinnati/Northern Kentucky region. Associations were tested at genotype, allele, and haplotype levels. A genomic control analysis was performed to check for spurious associations resulting from population substructure.
At the APOE locus, no individual SNP was associated with SAH after correction for multiple comparisons. Haplotype analysis revealed significant association of the major haplotype (Hap1) in APOE with SAH (p = 0.001). The association stemmed from both the 5' promoter and the 3' region of the APOE gene. APOE epsilon2 and epsilon 4 were not significantly associated with SAH. No association was observed for ELN at genotype, allele, or haplotype level and our study failed to confirm previous reports of ELN association with aneurysmal SAH.
This study suggests a role of the APOE gene in the etiology of aneurysmal SAH.
载脂蛋白E（APOE）和弹性蛋白（ELN）是参与中风发病机制的可能候选基因。我们在一项基于人群的研究中测试了APOE和ELN基因变异与蛛网膜下腔出血（SAH）的关联。我们对309名高加索个体样本中的APOE基因上的12个单核苷酸多态性（SNP）和ELN基因上的10个SNP进行了基因分型，其中107例为SAH病例，202例为来自大辛辛那提/北肯塔基地区的年龄、种族和性别匹配的对照。在基因型、等位基因和单倍型水平上测试了关联性。进行了基因组对照分析以检查由群体亚结构导致的虚假关联。
在APOE基因座，经多重比较校正后，没有单个SNP与SAH相关。单倍型分析显示APOE中的主要单倍型（Hap1）与SAH有显著关联（p = 0.001）。这种关联源于APOE基因的5'启动子和3'区域。APOE ε2和ε4与SAH无显著关联。在基因型、等位基因或单倍型水平上未观察到ELN与SAH的关联，并且我们的研究未能证实先前关于ELN与动脉瘤性SAH关联的报道。
本研究表明APOE基因在动脉瘤性SAH的病因学中起作用。
