The association of the regulatory region of the presenilin-2 gene with Alzheimer's disease in the Northern Han Chinese population

Presenilin-2 is one of the causative genes for familial Alzheimer's disease (FAD). Polymorphism of the promoter region of the presenilin-2 gene (PSEN2) has recently been reported in a Russian population to be associated with sporadic Alzheimer's disease (SAD). The purpose of this case-control study was to determine whether SAD is associated with the PSEN2 gene polymorphism in a Chinese population. We examined PSEN2 and APOE genotypes in 200 SAD patients and an equal number of age- and sex-matched controls from the same community, using the PCR–RFLP method. Allelic and genotypic distributions were performed using the Pearson Chi-square test for homogeneity. The interactions between variables were examined by logistic regression. The results revealed no significant differences in the frequency of the + A/− A polymorphism between AD and controls (χ2 = 3.857, p = 0.145). However, in the subgroup of APOE ɛ4 non-carriers, there were significant differences in the distributions of both alleles (χ2 = 6.095, p = 0.047) and genotypes (χ2 = 4.433, p = 0.035) of the PSEN2 promoter in AD compared with controls. In APOE ɛ4 non-carrier group, with + A/+ A as a reference, the − A/− A genotype was associated with a 4.657-fold increased risk for AD (χ2 = 5.783, p = 0.016, OR = 4.657, 95% CI = 1.195–18.152). Using logistic analysis, there were no statistical interactions between PSEN2 and APOE genotypes, or between PSEN2 genotypes and age of onset. It is concluded that in the Northern Han Chinese population, the + A/− A polymorphism of the PSEN2 promoter is a moderate genetic risk factor for developing SAD, independent of the APOE ɛ4 allele.