ALOX5AP gene and the PDE4D gene in a central European population of stroke patients
ALOX5AP gene and the PDE4D gene in a central European population of stroke patients
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DOI：
10.1161/01.str.0000157587.59821.87
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发表时间：
2005-04-01
期刊：
影响因子：
8.3
通讯作者：
Dichgans, M
中科院分区：
文献类型：
--
作者：
Lohmussaar, E;Gschwendtner, A;Dichgans, M
背景和目的-最近的证据表明，5-脂氧合酶激活蛋白(ALOX5AP)和磷酸二酯酶4D(PDE4D)基因是冰岛人群中风的易感基因。本研究的目的是探索这些基因在中欧中风患者群体中的作用。方法-采用病例对照设计，对639名连续的中风患者和736名年龄和性别匹配的基于人群的无关对照进行了研究。对覆盖ALOX5AP的22个单核苷酸多态(SNPs)进行了基因分型。对PDE4D的微卫星AC008818-1和12个SNPs进行了分析，它们标记了先前发现的连锁不平衡(LD)块中所有常见的单倍型。结果-ALOX5AP中的几个SNP与卒中存在名义上的显著关联，包括SNP SG13S114，它曾是冰岛高危单倍型的一部分。男性的关联性强于女性，SG13S114(优势比为1.24；95%可信区间为1.04-1.55；P=0.017)和SG13S100(优势比为1.26；95%可信区间为1.03-1.54；P=0.024)显示出最强的相关性。未发现与PDE4D的单标记和单倍型显著相关。单标记等位基因和单倍型的频率与冰岛人群有很大差异。结论--本研究提示ALOX5AP基因的序列变异与卒中显著相关，尤其是在男性。PDE4D基因的变异不是中欧人中风的主要风险因素。等位基因和单倍型频率以及LD结构的群体差异可能是造成群体间差异的原因之一。
Background and Purpose - Recent evidence has implicated the genes for 5-lipoxygenase activating protein (ALOX5AP) and phosphodiesterase 4D (PDE4D) as susceptibility genes for stroke in the Icelandic population. The aim of the present study was to explore the role of these genes in a central European population of stroke patients.Methods - A total of 639 consecutive stroke patients and 736 unrelated population-based controls that had been matched for age and sex were examined using a case-control design. Twenty-two single-nucleotide polymorphisms ( SNPs) covering ALOX5AP were genotyped. For PDE4D, microsatellite AC008818-1 and 12 SNPs, which tag all common haplotypes in previously identified linkage disequilibrium (LD) blocks, were analyzed.Results - A nominally significant association with stroke was observed with several SNPs from ALOX5AP, including SNP SG13S114, which had been part of the Icelandic at-risk haplotype. Associations were stronger in males than in females, with SG13S114 ( odds ratio, 1.24; 95% CI, 1.04 to 1.55; P = 0.017) and SG13S100 ( odds ratio, 1.26; 95% CI 1.03 to 1.54; P = 0.024) showing the strongest associations. No significant associations were detected with single markers and haplotypes in PDE4D. The frequencies of single-marker alleles and haplotypes differed largely from those in the Icelandic population.Conclusions - The present study suggests that sequence variants in the ALOX5AP gene are significantly associated with stroke, particularly in males. Variants in the PDE4D gene are not a major risk factor for stroke in individuals from central Europe. Population differences in allele and haplotype frequencies as well as LD structure may contribute to the observed differences between populations.