Association of polymorphisms in the apolipoprotein E region with susceptibility to and progression of multiple sclerosis
Association of polymorphisms in the apolipoprotein E region with susceptibility to and progression of multiple sclerosis
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DOI：
10.1086/339269
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发表时间：
2002-03-01
影响因子：
9.8
通讯作者：
Haines, JL
中科院分区：
文献类型：
--
作者：
Schmidt, S;Barcellos, LF;Haines, JL
多发性硬化症 (MS) 是一种中枢神经系统慢性炎症性疾病，其病因复杂，其中包括很强的遗传因素。主要组织相容性复合体 (MHC) 的贡献已在大量遗传连锁和关联研究中得到证实。除了 MHC 之外，在进行基于家族的分析时，载脂蛋白 E (APOE) 基因周围的染色体 19q13 区域也显示出与 MS 相关的一致证据。此外，一些临床报告表明 APOE-4 等位基因可能与更严重的疾病和更快的残疾进展有关。为了彻底检查 APOE 在 MS 中的作用，我们在 398 个家族的数据集中对其功能等位基因以及主要位于 APOE 13 kb 内的 7 个单核苷酸多态性 (SNP) 进行了基因分型。通过基于家族的关联分析，我们发现了具有统计学意义的证据，表明 APOE 附近的 SNP 单倍型与 MS 易感性相关 (P = .005)。对来自 379 个家庭的 614 名 MS 患者的疾病进展分析表明，APOE-4 携带者更有可能患有严重疾病 (P = .03)，而 APOE-2 携带者中较高比例的患者表现出轻度病程 (P = .02)。
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, with a complex etiology that includes a strong genetic component. The contribution of the major histocompatibility complex (MHC) has been established in numerous genetic linkage and association studies. In addition to the MHC, the chromosome 19q13 region surrounding the apolipoprotein E (APOE) gene has shown consistent evidence of involvement in MS when family-based analyses were conducted. Furthermore, several clinical reports have suggested that the APOE-4 allele may be associated with more-severe disease and faster progression of disability. To thoroughly examine the role of APOE in MS, we genotyped its functional alleles, as well as seven single-nucleotide polymorphisms (SNPs) located primarily within 13 kb of APOE, in a data set of 398 families. Using family-based association analysis, we found statistically significant evidence that an SNP haplotype near APOE is associated with MS susceptibility (P = .005). An analysis of disease progression in 614 patients with MS from 379 families indicated that APOE- 4 carriers are more likely to be affected with severe disease (P = .03), whereas a higher proportion of APOE- 2 carriers exhibit a mild disease course (P = .02).