Joint analysis of candidate genes related to Alzheimer's disease in a Spanish population

Background Besides the repeated association between the epsilon4 allele of the apolipoprotein E and Alzheimer's disease, several candidate genes have been analysed with inconsistent results. Most of these studies have examined only one or two polymorphisms in a defined population, which provides a lack of a general view of the Alzheimer's disease genetic component. Objective To overcome this limitation, nine polymorphisms in seven different candidate genes (A2M, ACT, APOE, APP, BH, HSP70-2, and IL1-A) were genotyped. Methods The sample comprised 112 Alzheimer's disease patients and 89 controls from Spain. Since haplotype reconstruction may add power to association studies, we also tested for linkage disequilibrium within the A2M and APOE genes. Results Except for the APOE gene, allele and genotype frequencies were not different between cases and controls, even when stratifying for the APOE genotype. Conclusion The present results suggest that future association studies should be performed using a battery of polymorphisms in different and new candidate genes, taking into account the linkage disequilibrium in the region. (C) 2003 Lippincott Williams Wilkins.