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  • Title: The GAB2 gene and the risk of Alzheimer's disease: replication and meta-analysis.
    Author: Ikram MA, Liu F, Oostra BA, Hofman A, van Duijn CM, Breteler MM.
    Journal: Biol Psychiatry; 2009 Jun 01; 65(11):995-9. PubMed ID: 19118819.
    Abstract:
    BACKGROUND: Recently, GAB2 has been suggested to modify the risk of late-onset Alzheimer's disease (AD) among APOEepsilon4 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 APOEepsilon4 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 APOEepsilon4 carriers.
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