APOE promoter polymorphisms do not confer independent risk for Alzheimer'sdisease in a French population

The apolipoprotein E (APOE, gene; apoE, protein) isoforms are associated wi th differential risk of Alzheimer's disease (AD). An additional involvement of APOE promoter polymorphisms in AD risk has recently been suggested by s everal studies. Indeed, three polymorphisms of the APOE regulatory region ( -219 G/T, -427 C/T and -491 A/T) have been found associated with AD even af ter adjustment on the apoE status. We analysed these three promoter region polymorphisms in a large French case-control study (388 AD cases and 386 co ntrols). We found that the -427 T and -491 A alleles were associated with a n increased risk of developing AD, but not the -219 C/T alleles. However, a strong linkage disequilibrium was observed between the alleles of these pr omoter region polymorphisms and the APOE coding region alleles. We therefor e retested association after adjustment on apoE status and found that the s ole association which remained significant was the association with the -42 7T allele. The alpha level was equal to 0.03 (0.09 after Bonferroni correct ion for multiple comparisons). Analysis of promoter haplotypes also yielded non-significant results. Thus our study does not reinforce the hypothesis of an independent involvement of the APOE promoter region polymorphisms in AD risk.