1. Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease
- Author
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J. Liang, Iman Azam Ghavami, E. Cocchi, D. Chatterjee, J. Zhang, R. Gras, Ali G. Gharavi, M. M. Morban, G. Lab, A. Mo, J. Zheng, K. O. Stevens, J. Lewis, Maddalena Marasa, Stacy Piva, J. S. Kim, G. Jin, Byum Hee Kil, V. M. Nicasio, and M. Elliott
- Subjects
Male ,0301 basic medicine ,Transcription, Genetic ,030232 urology & nephrology ,Apoptosis ,urologic and male genital diseases ,medicine.disease_cause ,Genetic analysis ,Serology ,Mice ,Liver disease ,0302 clinical medicine ,Catalytic Domain ,RNA-Seq ,Exome ,Fisher's exact test ,Mice, Knockout ,General Medicine ,Polycystic Kidney, Autosomal Dominant ,female genital diseases and pregnancy complications ,Phenotype ,Nephrology ,embryonic structures ,Cohort ,symbols ,Medical genetics ,Female ,DNA Replication ,medicine.medical_specialty ,TRPP Cation Channels ,03 medical and health sciences ,symbols.namesake ,Internal medicine ,CDC2 Protein Kinase ,Exome Sequencing ,medicine ,Animals ,Crosses, Genetic ,Cell Proliferation ,urogenital system ,business.industry ,Gene Expression Profiling ,Pyruvate Dehydrogenase Acetyl-Transferring Kinase ,Immune dysregulation ,medicine.disease ,Mice, Inbred C57BL ,Basic Research ,030104 developmental biology ,Gene Expression Regulation ,Mutation ,business - Abstract
Background: Patients with preexisting chronic kidney (CKD) and liver disease and liver are more at risk from COVID-19, but reasons for variability in disease susceptibility and severity is still poorly understood. Given the high infection rate in New York City, we conducted a COVID-19 assessment survey in a cohort of CKD and liver patients previously consented into genetic studies. Methods: Between March and August 2020, we completed 1601 unique IRBapproved COVID-19 assessment surveys. The survey covered COVID-19 symptoms, exposure risk, PCR and/or serology testing, and hospitalization. 298 of those patients were exome sequenced. We analyzed differences in COVID-19 PCR, serology and hospitalization rate and genetic analysis to identify possibly associated variants in the immune/coagulation pathways, suggested to be involved in COVID-19 susceptibility/ severity by recent publicationw. We also analyzed variants based on the American College of Medical Genetics and Genomics (ACMG) guidelines for clinical annotation of genetic results Results: Hispanic/Latino patients were more likely to have a positive COVID-19 PCR (Fisher Exact Test p: 0.01, 29.5% vs 16.7%), serology (Fisher Exact Test p: 0.02, 22.9% vs 9.7%) and hospitalization (Fisher Exact Test p: 0.01, 29.5% vs 16.7%). Patients with glomerulopathy had lower positive COVID-19 PCR tests (Fisher Exact Test p: 0.01, 14.7% vs 48.7%). Analysis of exome data identified an excess number of rare variants in genes in the immune dysregulation pathways among patients with positive COVID-19 PCR test, (fisher p: 0.01, 75% vs 18%). These results were mostly driven by rare variants in CASP10, which were more common among the Hispanic/Latino population. Conclusions: We confirm that Hispanic/Latino ethnicity is a significant risk factor for positive COVID-19 PCR, serology and hospitalization. The analysis of the genetic mechanisms in immune/coagulation pathways identified an excess of rare variants in the CASP10 gene, results that overlap with Hispanic/Latino ethnicity.
- Published
- 2020
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