Association between the ABCG2 C421A polymorphism and Alzheimer's disease

ATP binding cassette subfamily G member 2 (ABCG2) is involved in amyloid-β transport and was found to be significantly up-regulated in Alzheimer's disease (AD) brain. A functional polymorphism of the ABCG2 gene (C421A; rs2231142) was genotyped in a sample of 299 Hungarian late-onset AD patients and 259 elderly, non-demented controls to investigate for the first time its association with AD, either alone or in combination with apolipoprotein E (APOE) ɛ2/ɛ3/ɛ4 polymorphism. A significantly increased susceptibility to AD (OR = 1.741, 95% CI: 1.075-2.819, p = 0.024) associated with ABCG2 C/C genotype was found when compared with the variant allele containing genotypes (CA and AA) as the reference category. Logistic regression analysis revealed a significant interaction effect between the ABCG2 C/C genotype and APOE ɛ4 allele on AD risk (p = 0.003). It seems that the potential modest risk effect of the ABCG2 C/C genotype on AD risk is more pronounced in combination with the APOE ɛ4 allele. Further independent replications of our findings are required.