BIN1 rs744373 SNP and COVID-19 mortality

Area of Science:

• Genetics and Infectious Disease Epidemiology
• Molecular Biology and Bioinformatics

Background:

• Apolipoprotein E (APOE) e4 genotype is a known risk factor for Alzheimer's disease (AD) and severe COVID-19.
• Bridging integrator 1 (BIN1) gene single nucleotide polymorphisms (SNPs) are the second highest risk factor for sporadic AD.
• The influence of BIN1 variants on COVID-19 survival remains largely unexplored.

Purpose of the Study:

• To investigate the association between BIN1 gene variants (specifically SNP rs744373) and COVID-19 related survival.
• To analyze the interaction and molecular alignment between BIN1 and SARS-CoV-2 proteins.

Main Methods:

• Utilized UK Biobank (UKB) data to analyze the effects of BIN1 alleles (designated BIN and RS7) on COVID-19 mortality.
• Employed logistic regression analysis with survival/mortality as the dependent variable, considering sex, age, genotype, AD, and coronary heart disease (CHD) as independent variables.
• Performed protein molecule alignment analysis using Protein Data Bank (PDB) entries to assess BIN1 and SARS-CoV-2 interactions.

Main Results:

• The BIN1 RS7 heterozygote genotype was associated with the lowest COVID-19 mortality rate (11.7%).
• The BIN1 BIN homozygote had a mortality rate of 17.2%, while the RS7 RS7 homozygote exhibited the highest rate (28.1%).
• Male sex and older age significantly increased COVID-19 mortality risk; AD and CHD effects were insignificant. Protein alignment suggested BIN allele interference with SARS-CoV-2 replication.

Conclusions:

• COVID-19 mortality risk is influenced by Alzheimer's disease-associated genes, particularly BIN1 variants, independent of chronological age and common comorbidities.
• Specific BIN1 genotypes, like the RS7 heterozygote, are linked to reduced COVID-19 mortality.
• The BIN1 allele may possess a protective mechanism against SARS-CoV-2 replication, warranting further investigation.