AUTHOR=Cachide Maria , Carvalho Liliana , Rosa Ilka Martins , Wiltfang Jens , Henriques Ana Gabriela , da Cruz e Silva Odete A. B. 

TITLE=BIN1 rs744373 SNP and APOE alleles specifically associate to common diseases

JOURNAL=Frontiers in Dementia

VOLUME=1

YEAR=2022

URL=https://www.frontiersin.org/journals/dementia/articles/10.3389/frdem.2022.1001113

DOI=10.3389/frdem.2022.1001113

ISSN=2813-3919

ABSTRACT=<p><italic>APOE</italic> ε4 and <italic>BIN1</italic> are the two main genetic risk factors for sporadic Alzheimer's Disease (AD). Among several <italic>BIN1</italic> variants, the rs744373 is frequently associated with AD risk by contributing to tau pathology and poor cognitive performance. This study addressed the association of <italic>APOE</italic> and <italic>BIN1</italic> rs744373 to specific characteristics in a Portuguese primary care-based study group, denoted pcb-Cohort. The study included 590 participants from five primary care health centers in the Aveiro district of Portugal. Individuals were evaluated and scored for cognitive and clinical characteristics, and blood samples were collected from the volunteers meeting the inclusion and exclusion criteria (<italic>N</italic> = 505). <italic>APOE</italic> and <italic>BIN1</italic> genotypes were determined, and their association with cognitive characteristics and other diseases that might contribute to cognitive deficits, namely depression, hypertension, type 2 diabetes, dyslipidemia, osteoarticular diseases, gastrointestinal diseases, cardiovascular and respiratory diseases, was assessed. The diseases attributed to the study group were those previously diagnosed and confirmed by specialists. The results generated through multivariate analysis show that <italic>APOE</italic> ε4 carriers significantly associated with poorer cognitive performance (OR = 2.527; <italic>p</italic> = 0.031). Additionally, there was a significant risk of dyslipidemia for <italic>APOE</italic> ε4 carriers (OR = 1.804; <italic>p</italic> = 0.036), whereas <italic>BIN1</italic> rs744373 risk-allele carriers were at a significantly lower risk of having dyslipidemia (OR = 0.558; <italic>p</italic> = 0.006). Correlations were evident for respiratory diseases in which <italic>APOE</italic> ε4 showed a protective tendency (OR = 0.515; <italic>p</italic> = 0.088), and <italic>BIN1</italic> had a significative protective profile (OR = 0.556; <italic>p</italic> = 0.026). Not of statistical significance, <italic>APOE</italic> ε2 showed a trend to protect against type 2 diabetes (OR = 0.342; <italic>p</italic> = 0.093), in contrast <italic>BIN1</italic> rs744373 risk-allele carriers were more likely to exhibit the disease (OR = 1.491; <italic>p</italic> = 0.099). The data here presented clearly show, for the first time, that the two top genetic risk factors for sporadic AD impact a similar group of common diseases, namely dyslipidemia, respiratory diseases, and type 2 diabetes.</p>