Lehrer Steven, Rheinstein Peter H
Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Severn Health Solutions, Severna Park, MD 21146, USA.
World Acad Sci J. 2021 Mar-Apr;3(2). doi: 10.3892/wasj.2021.84. Epub 2021 Jan 14.
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 and the SNP rs744373 minor (Alzheimer's) allele as . 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.
载脂蛋白E(APOE)e4基因型会增加患阿尔茨海默病(AD)的风险,在一个英国生物银行(UKB)队列中,它预示着严重的2019冠状病毒病(COVID-19)感染。桥连整合器1(BIN1)基因中的单核苷酸多态性(SNP)表明其在散发性AD中的优势比仅次于APOE变异,位列第二。本研究的目的是利用源自UKB的数据评估BIN1和单核苷酸多态性rs744373对COVID-19相关生存的影响。此外,还评估了BIN1与严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的相互作用和比对情况。为此,将主要的(非阿尔茨海默病相关的)BIN1等位基因指定为 ,将单核苷酸多态性rs744373的次要(阿尔茨海默病相关的)等位基因指定为 。为了评估BIN1与SARS-CoV-2的相互作用和比对情况,在RCSB蛋白质数据库中搜索了蛋白质数据库(pdb)条目。结果显示,BIN RS7杂合子的死亡率最低(11.7%),其次是BIN BIN纯合子(17.2%)。RS7 RS7纯合子的死亡率最高(28.1%)。还以生存或死亡为因变量,性别、年龄、基因型、AD和冠心病(CHD)为自变量进行了逻辑回归分析。性别、年龄和基因型的影响在95%的水平上具有显著性。男性和老年受试者比女性和年轻受试者更易死于经检测确诊的COVID-19。AD和CHD的影响不显著。蛋白质分子比对分析表明,BIN等位基因可能会干扰SARS-CoV-2病毒的复制。本研究结果表明,COVID-19死亡风险不仅与实际年龄较大或老年受试者中常见的合并症(如CHD和AD)有关,还与AD基因有关。