BIN1 rs744373 SNP and COVID-19 mortality.

Abstract

Apolipoprotein E (APOE) e4 genotype, which increases the risk of Alzheimer’s disease (AD), predicted severe COVID-19 infection in one UK Biobank (UKB) cohort. Single nucleotide polymorphisms (SNPs) in the bridging integrator 1 (BIN1) gene indicate the second highest odds-ratios for sporadic AD, exceeded only by APOE variants. The objective of the present study was to evaluate the effects of BIN1 and the SNP rs744373 on COVID-19-relaetd survival using UKB-derived data. In addition, the interaction and alignment of BIN1 and SARS-Cov-2 were evaluated. For this purpose, the major (non-Alzheimer’s) BIN1 allele was designated as BIN and the SNP rs744373 minor (Alzheimer’s) allele as RS7. To evaluate the interaction and alignment of BIN1 and SARS-Cov-2, Protein Data Bank (pdb) entries were searched on the RCSB Protein Data Bank. The results revealed that the BIN RS7 heterozygote was associated with the lowest mortality rate (11.7%), followed by the BIN BIN homozygote (17.2%). The RS7 RS7 homozygote was associated with the highest mortality rate (28.1%). Logistic regression analysis was also performed using survival or mortality as the dependent variable, and sex, age, genotype, AD and coronary heart disease (CHD) as independent variables. The effects of sex, age and genotype were significant at the 95% level. The male sex and older-aged subjects were more likely to succumb to test-confirmed COVID-19 than females and younger subjects. The effects of AD and CHD were insignificant. Protein molecule alignment analyses suggested that the BIN allele may interfere with the replication of the SARs-Cov2 virus. The findings of the present study demonstrate that the risks for COVID-19 mortality are not simply related to an advanced chronological age or the comorbidities commonly observed in aged subjects, such as CHD and AD, but also with AD genes.