Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease
Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease
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DOI：
10.1016/j.jns.2006.05.043
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发表时间：
2006-09-25
影响因子：
4.4
通讯作者：
Mecocci, Patrizia
中科院分区：
文献类型：
--
作者：
Mariani, Elena;Seripa, Davide;Mecocci, Patrizia
CTSD基因编码的蛋白质组织蛋白酶D和A2 M基因编码的α 2-巨球蛋白参与导致β-淀粉样蛋白沉积的生化途径。在这些蛋白质中，两个氨基酸多态性（CTSD-Ala/瓦尔C -> T和A2 M-Ile/vat A -> G）与阿尔茨海默病（AD）的风险增加相关，但已报道了相互矛盾的结果。我们研究了100例晚发性AD患者和136例健康老年人的CTSD-C/T和A2 M-A/G多态性与散发性AD的相关性和相互作用。CTSD-T等位基因和CTSD-C/T基因型在AD组中的频率显著高于对照组。CTSD-T受试者的比值比（OR）为1.93 [95%置信区间（CI）=1.01-3.72]，校正年龄、性别和APOE β 4+状态后为2.07（95% CI=1.01-4.21），而A2 M-A/G多态性未发现显著相关性。CTSD-T与A2 M-G等位基因的共存使AD的OR协同增加至2.69（95% CI=1.13-6.34）[校正后为2.82（95% CI=1.12-7.17）]，如果估计等位基因组合，则增加至3.29（95% CI=1.33-8.16）。我们的数据表明，CTSD-C/T多态性的CTSD-T等位基因与迟发性AD的相对风险增加相关，更有趣的是，CTSD-T与A2 M-G等位基因的组合似乎增加了这种风险。(c)2006 Elsevier B. V.保留所有权利。
The proteins cathepsin D, encoded by CTSD gene, and alpha(2)-macroglobulin, encoded by A2M gene, are involved in the biochemical pathway leading to deposition of beta-amyloid. In these proteins two amino acid polymorphisms (CTSD-Ala/Val C -> T and A2M-Ile/vat A -> G) have been associated with an increased risk for Alzheimer's disease (AD), but conflicting results have been reported. We studied the association and the mutual interactions of the CTSD-C/T and A2M-A/G polymorphisms with sporadic AD in 100 patients with late-onset AD and 136 healthy elderly subjects as controls. The CTSD-T allele and the CTSD-C/T genotype are significantly more frequent in AD than in controls. The odds ratio (OR) for CTSD-T subjects is 1.93 [95% confidence interval (CI)=1.01-3.72], and 2.07 (95% CI=1.01-4.21) after adjustment for age, sex and APOE epsilon 4+ status, while no significant association was found for the A2M-A/G polymorphism. The coexistence of the CTSD-T with the A2M-G allele synergistically increased the OR for AD to 2.69 (95% CI=1.13-6.34) [2.82 (95% CI=1.12-7.17) after adjustment], and to 3.29 (95% CI=1.33-8.16) if estimated for the allelic combination. Our data suggest that the CTSD-T allele of the CTSD-C/T polymorphism is associated with an increased relative risk for late-onset AD and, more interestingly, the combination of CTSD-T with the A2M-G allele seems to increase this risk. (c) 2006 Elsevier B.V. All rights reserved.