Variants in an Iberian Alzheimer Cohort Detected through an Optimized Sanger Sequencing Protocol.

The primary genetic risk factor for late onset Alzheimer's disease (LOAD) is the allele of () gene. The three most common variants of are determined by single nucleotide polymorphisms (SNPs) rs429358 and rs7412. Our aim was to estimate allele and genotype frequencies of variants in an Iberian cohort, thus helping to understand differences in -related LOAD risk observed across populations. We analyzed saliva or buccal swab samples from 229 LOAD patients and 89 healthy elderly controls (≥68 years old) from Northern Portugal and Castile and León region, Spain. The genotyping was performed by Sanger sequencing, optimized to overcome GC content drawbacks. Results obtained in our Iberian LOAD and control cohorts are in line with previous large meta-analyses on frequencies in Caucasian populations; however, we found differences in allele frequencies between our Portuguese and Spanish subgroups of AD patients. Moreover, when comparing studies from Iberian and other Caucasian cohorts, differences in and frequencies and subsequent different -related LOAD risks must be clarified. These results show the importance of studying genetic variation at the gene in different populations (including analyses at a regional level) to increase our knowledge about its clinical significance.