The ATP-binding cassette, subfamily A, member 7 gene (ABCA7) was recently identified as a susceptible gene of Alzheimer's disease (AD) in the Caucasian population and African Americans. To test its genetic effect in the Han-Chinese population, 536 AD cases and 307 cognitive-intact, elder controls were genotyped for ABCA7 rs3764650 and apolipoprotein E (APOE) ε2/ε3/ε4 alleles. Global cognitive performance was assessed by the Mini-Mental State Examination in both AD patients and controls. For AD patients, comprehensive evaluation of each cognitive domain was further conducted as the following: (1) attention (forward and backward digit span); (2) memory (12-item word recall test); (3) executive function (category verbal fluency); (4) processing speed (Trail making test, part A); and (5) naming task (Boston naming test). ABCA7 rs3764650 was significantly associated with AD and the GG genotype carried a reduced risk for AD (odds ratio = 0.52, p = 0.0026). The association was further confirmed in 1802 population-based, healthy controls from Taiwan Biobank as a replicate (odds ratio = 0.70, p = 0.032). After adjustment of age, sex, and APOE ε4 allele, rs3764650 remained to be an independent predictor of AD (p = 0.001). The influence of ABCA7 was only evident in individuals without APOE ε4 alleles (p = 0.0004) but absent in ε4 carriers (p = 0.91). None of the cognitive tests was related to ABCA7 rs3764650 genotypes. The minor allele frequency and effect size of rs3764650 disclosed in the Han-Chinese population differed from those reported in the Caucasians and African Americans. Further studies were warranted to elucidate ABCA7's effect among different ethnic groups.
Keywords: ABCA7 gene; APOE ε4 allele; Alzheimer's disease; Genetic interaction.
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