GAB2 GENE DOES NOT MODIFY THE RISK OF ALZHEIMER'S DISEASE IN SPANISH APOE 4 CARRIERS
GAB2 GENE DOES NOT MODIFY THE RISK OF ALZHEIMER'S DISEASE IN SPANISH APOE 4 CARRIERS
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DOI：
10.1007/s12603-009-0061-6
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发表时间：
2009-03-01
影响因子：
5.8
通讯作者：
Ruiz, A.
中科院分区：
文献类型：
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作者：
Ramirez-Lorca, R.;Boada, M.;Ruiz, A.
目的：多项全基因组关联研究 (WGAS) 正在分析阿尔茨海默病 (AD) 的遗传基础。最近在美国进行的病例对照 WGAS 中，GAB2 基因被提议作为 APOE epsilon 4 等位基因的修饰因子。鉴于这些新结果在 AD 诊断中的潜在应用，我们决定进行独立复制以检查我们系列中的 GAB2 基因效应。设计：我们正在西班牙进行一项基于人群的多中心 AD 研究。参与者：我们总共分析了 1116 名西班牙人。具体来说，521 名 AD 患者、475 名普通人群对照者和 120 名神经功能正常的老年对照者（NNE 对照）。方法：我们使用实时 PCR 技术对 GAB2 (rs2373115 G/T) 和 APOE rs429358 (SNP112)/rs7412 (SNP158) 多态性进行基因分型。结果：正如之前在西班牙报道的，APOE epsilon 4 等位基因与我们系列中的 AD 密切相关（OR=2.88 [95% C.I. 2.16-3.84]，p=7.38E-11）。此外，还观察到 epsilon 4/ epsilon 4 基因型有很大影响（OR=14.45 [ 95% C. I., 3.34-125.2]，p=1.8E-6）。一般人群和 NNE 对照系列之间的 APOE 基因型没有观察到差异（P>0.61）。接下来，我们使用不同的遗传模型探索了 GAB2 rs2373115 SNP 单基因座关联，并将 AD 与对照或 NNE 对照进行比较。没有观察到该 GAB2 标记物与 AD 相关的证据 (p>0.17)。为了评估 GAB2-APOE 基因间相互作用，我们根据原始研究，根据 APOE 基因型和病例对照状态对我们的系列进行了分层。同样，在 GAB2-APOE 基因座对的任何层中均未观察到与 AD 遗传相关的证据 (p>0.34)。结论：GAB2 rs2373115 标记不会改变西班牙 APOE epsilon 4 携带者患阿尔茨海默病的风险。
Objectives: The genetic basis of Alzheimer's disease (AD) is being analyzed in multiple whole genome association studies (WGAS). The GAB2 gene has been proposed as a modifying factor of APOE epsilon 4 allele in a recent case-control WGAS conducted in the US. Given the potential application of these novel results in AD diagnostics, we decided to make an independent replication to examine the GAB2 gene effect in our series. Design: We are conducting a multicenter population-based study of AD in Spain. Participants: We analyzed a total of 1116 Spanish individuals. Specifically, 521 AD patients, 475 controls from the general population and 120 neurologically-normal elderly controls (NNE controls). Methods: We have genotyped GAB2 (rs2373115 G/T) and APOE rs429358 (SNP112)/rs7412 (SNP158) polymorphisms using real time-PCR technologies. Results: As previously reported in Spain, APOE epsilon 4 allele was strongly associated with AD in our series (OR=2.88 [95% C.I. 2.16-3.84], p=7.38E-11). Moreover, a large effect for epsilon 4/ epsilon 4 genotype was also observed (OR=14.45 [ 95% C. I., 3.34-125.2], p=1.8E-6). No difference between the general population and the NNE controls series were observed for APOE genotypes (P>0.61). Next, we explored GAB2 rs2373115 SNP single-locus association using different genetic models and comparing AD versus controls or NNE controls. No evidence of association with AD was observed for this GAB2 marker (p>0.17). To evaluate GAB2-APOE gene-gene interactions, we stratified our series according to APOE genotype and case-control status, in accordance with the original studies. Again, no evidence of genetic association with AD was observed in any strata of GAB2-APOE loci pair (p>0.34). Conclusion: GAB2 rs2373115 marker does not modify the risk of Alzheimer's disease in Spanish APOE epsilon 4 carriers.