Desai PP, Hendrie HC, Evans RM, Murrell JR, DeKosky ST, Kamboh MI. Genetic variation in apolipoprotein D affects
the risk of Alzheimer disease in African-Americans. Am J Med Genet 2003;116(1 Suppl):98-101.
Apolipoprotein D (APOD, gene; apoD, protein) is involved in neuroregenerative and neurodegenerative processes, and
is upregulated in late-onset Alzheimer disease (AD) patients compared to nondemented controls. No genetic association
studies have yet been carried out to investigate the role of APOD in AD. We have reported recently several sequence
variants in the APOD gene, which are present exclusively among African blacks. In the present study we examined the
role of four APOD genetic variants (Intron 1, codons 36, 108, 158) in modifying the risk of AD in 70 subjects with
AD and 163 nondemented subjects from a population-based African-American cohort in Indianapolis. The Intron 1*2 allele
was associated with an increased AD risk with an age, gender and APOE adjusted odds ratio (OR) of 2.29 (95% confidence
interval [CI]: 1.19-4.43; P = 0.013), and this risk was confined to APOE*4 carriers (OR 3.12; 95% CI: 1.13-8.60; P =
0.028). The frequency of the codon 36/GT genotype was non-significantly higher in individuals with AD than nondemented
subjects (4.3% vs. 1.2%) with an adjusted OR of 4.24 (95% CI: 0.66-27.14; P = 0.13). Our data suggest that the risk of
AD among African-Americans may be modified by genetic variation in APOD. Larger population-based or case-control studies
are needed to confirm the role of APOD genetic variation in AD. Copyright 2002 Wiley-Liss, Inc.
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