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

Abstract

The primary genetic risk factor for late onset Alzheimer’s disease (LOAD) is the APOE4 allele of Apolipoprotein E (APOE) gene. The three most common variants of APOE are determined by single nucleotide polymorphisms (SNPs) rs429358 and rs7412. Our aim was to estimate allele and genotype frequencies of APOE variants in an Iberian cohort, thus helping to understand differences in APOE-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 APOE 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 APOE2 and APOE4 frequencies and subsequent different APOE-related LOAD risks must be clarified. These results show the importance of studying genetic variation at the APOE gene in different populations (including analyses at a regional level) to increase our knowledge about its clinical significance.

Long-covid cognitive impairment: Cognitive assessment and apolipoprotein E (APOE) genotyping correlation in a Brazilian cohort

“…To correlate a possible genetical predisposition and a significant risk of developing cognitive impairment, we performed an APOE genotyping for SNPs rs429358 and rs7412 in those patients, which are widely discussed in the literature as responsible for increasing the risk of dementia and cognitive impairment ( 39 – 42 ). APOEs play a vital role in lipid transport and metabolism, thus influencing the risk of cardiovascular disease ( 10 ).…”

Genetic and Environmental Factors in Ageing and Age-Related Disease

“…The major single genetic risk factor for late-onset Alzheimer’s disease is the apolipoprotein ( APOE ) ε4 allele. In addition to optimising APOE sequencing, Gonzalez et al [ 5 ] found allele differences in the ε4 and ε2 alleles in late-onset Alzheimer’s disease cases between Spanish and Portuguese subsamples, highlighting the importance of considering different ancestries and diverse populations when undertaking these studies.…”