Genetic variation in apolipoprotein D affects the risk of Alzheimer disease in African-Americans
Genetic variation in apolipoprotein D affects the risk of Alzheimer disease in African-Americans
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DOI：
10.1002/ajmg.b.10798
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Kamboh, MI
中科院分区：
文献类型：
--
作者：
Desai, PP;Hendrie, HC;Kamboh, MI
载脂蛋白D（APOD，基因; apoD，蛋白质）参与神经再生和神经退行性过程，并且与非痴呆对照相比，在迟发性阿尔茨海默病（AD）患者中上调。尚未进行遗传关联研究来调查A-POD在AD中的作用。我们最近报道了APOD基因的几个序列变异，这些变异只存在于非洲黑人中。在本研究中，我们研究了四个APOD基因变异（内含子1，密码子36，108，158）在修改AD的风险在70例AD和163例非痴呆症患者从人口为基础的非裔美国人在印第安纳波利斯队列中的作用。内含子1*2等位基因与AD风险增加相关，经年龄、性别和APOE校正的比值比（OR）为2.29（95%置信区间[CI]：1.19-4.43; P=0.013），且该风险仅限于APOE*4携带者（OR 3.12; 95% CI：1.13-8.60; P = 0.028）。AD患者密码子36/GT基因型的频率非显著性高于非痴呆受试者（4.3%vs.1.2%），校正OR为4.24（95%CI：0.66-27.14; P=0.13）。我们的数据表明，在非裔美国人中AD的风险可能是由APOD的遗传变异修改。需要更大的基于人群或病例对照研究来证实APOD遗传变异在AD中的作用。(C)2003 Wiley-Liss，Inc.
Apolipoprotein D (APOD, gene; apoD, protein) is involved in neuroregenerative and neurodegenerative processes, and is upregulated in late-onset Alzheimer disease (AD) patients compared to nondemented controls. No genetic association studies have yet been carried out to investigate the role of A-POD in AD. We have reported recently several sequence variants in the APOD gene, which are present exclusively among African blacks. In the present study we examined the role of four APOD genetic variants (Intron 1, codons 36, 108, 158) in modifying the risk of AD in 70 subjects with AD and 163 nondemented subjects from a population-based African-American cohort in Indianapolis. The Intron 1*2 allele was associated with an increased AD risk with an age, gender and APOE adjusted odds ratio (OR) of 2.29 (95% confidence interval [CI]: 1.19-4.43; P=0.013), and this risk was confined to APOE*4 carriers (OR 3.12; 95% CI: 1.13-8.60; P = 0.028). The frequency of the codon 36/GT genotype was non-significantly higher in individuals with AD than nondemented subjects (4.3% vs. 1.2%) with an adjusted OR of 4.24 (95% Cl: 0.66-27.14; P=0.13). Our data suggest that the risk of AD among African-Americans may be modified by genetic variation in APOD. Larger population-based or case-control studies are needed to confirm the role of APOD genetic variation in AD. (C) 2003 Wiley-Liss, Inc.