Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age-matched controls

Alzheimer disease (AD) is an emotionally devastating and exceptionally cost ly disease. Apolipoprotein E (APOE) is a major risk factor gene for AD rega rdless of age of onset or family history. However, this association may not be as strong or consistent in ethnic groups such as African Americans, rai sing the possibility of other modifier gene(s). In a group of African Ameri can AD patients, a significantly increased risk of AD was associated with t wo E4 alleles (OR = 5.6; 95% CI = 1.5-21.0) or one E4 allele (OR = 2.5; 95% CI = 1.3-5.0) when compared to E3/E3 genotype, and there was a significant lowering of age of onset for affecteds with E4/E4 genotype as compared to one E2 allele (P = 0.02) or all others (P = 0.03). We also found a signific ant increase in age of onset with the -308 #2 (A) allele of TNF when compar ed to AD cases with no #2 allele. A significant increase in age was also de monstrated with the #2 allele (99 base pairs) of the microsatellite TNFa, l ocated similar to 10.5 kb upstream of TNF. When these two alleles were comb ined with the TNF -238G; (#1) allele to give a haplotype, the significant i ncrease in age was still demonstrated. Polymorphisms in the APOE promoter a nd six other candidate genes did not appear to demonstrate any significant association with our African American AD patients. Our results confirm the established association of APOE4 to AD observed in several ethnic groups, i ncluding African Americans. In addition, TNF appears to have some modifying effect in AD, primarily on age of onset, or it could be in linkage disequi librium with a modifier locus nearby. (C) 2001 Wiley-Liss, Inc.