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The GAB2 Gene and the Risk of Alzheimer's Disease: Replication and Meta-Analysis

2009; Elsevier BV; Volume: 65; Issue: 11 Linguagem: Inglês

10.1016/j.biopsych.2008.11.014

1873-2402

M. Arfan Ikram, Fan Liu, Ben A. Oostra, Albert Hofman, Cornelia M. van Duijn, Monique M.B. Breteler,

Mitochondrial Function and Pathology

Background Recently, GAB2 has been suggested to modify the risk of late-onset Alzheimer's disease (AD) among APOEε4 carriers. However, replication data are inconsistent. Methods In a population-based cohort study (n = 5507; age > 55) with 443 incident AD cases, we investigated the association between rs4945261 and AD. Because we used high-density genotyping, we also investigated other polymorphisms within and around GAB2 and performed a meta-analysis with published studies. Results We found that rs4945261 was associated with AD among APOEε4 carriers (p = .02) but not among noncarriers (p = .26). Fifteen of the 20 remaining polymorphisms within GAB2 and several polymorphisms in the 250kbp-region surrounding GAB2 were also associated with AD among carriers and only one among noncarriers. For rs2373115, meta-analysis yielded an odds ratio of 1.58 (1.17–2.14) with p = 3.0 * 10–3 among carriers and 1.09 (.97–1.23) with p = .16 among noncarriers. For rs4945261, the pooled odds ratio was 1.75 (1.21–2.55) with p = 3.0 * 10–3 among carriers and 1.20 (1.01–1.41) with p = .03 among noncarriers. Conclusions We found GAB2 to be associated with AD. Furthermore, the meta-analysis also suggests that GAB2 modifies the risk of AD in APOEε4 carriers. Recently, GAB2 has been suggested to modify the risk of late-onset Alzheimer's disease (AD) among APOEε4 carriers. However, replication data are inconsistent. In a population-based cohort study (n = 5507; age > 55) with 443 incident AD cases, we investigated the association between rs4945261 and AD. Because we used high-density genotyping, we also investigated other polymorphisms within and around GAB2 and performed a meta-analysis with published studies. We found that rs4945261 was associated with AD among APOEε4 carriers (p = .02) but not among noncarriers (p = .26). Fifteen of the 20 remaining polymorphisms within GAB2 and several polymorphisms in the 250kbp-region surrounding GAB2 were also associated with AD among carriers and only one among noncarriers. For rs2373115, meta-analysis yielded an odds ratio of 1.58 (1.17–2.14) with p = 3.0 * 10–3 among carriers and 1.09 (.97–1.23) with p = .16 among noncarriers. For rs4945261, the pooled odds ratio was 1.75 (1.21–2.55) with p = 3.0 * 10–3 among carriers and 1.20 (1.01–1.41) with p = .03 among noncarriers. We found GAB2 to be associated with AD. Furthermore, the meta-analysis also suggests that GAB2 modifies the risk of AD in APOEε4 carriers.