دورية أكاديمية
Vascular calcification in chronic kidney disease associated with pathogenic variants in ABCC6.
| العنوان: | Vascular calcification in chronic kidney disease associated with pathogenic variants in ABCC6. |
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| المؤلفون: | Schott C; Department of Biochemistry, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada. Electronic address: cschott2@uwo.ca., Dilliott AA; Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, 845 Sherbrooke Street, West Montreal, QC H3A 0G4, Canada., Wang J; Robarts Research Institute, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 3K7, Canada., McIntyre AD; Robarts Research Institute, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 3K7, Canada., Son S; Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Colaiacovo S; Division of Medical Genetics, Department of Pediatrics, Victoria Hospital, London Health Science Center, 800 Commissioners Rd E, London, ON N6A 5W9, Canada., Baker C; London Health Sciences Centre, 339 Windermere Rd, London N6A 3K7, ON, Canada., Gunaratnam L; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., House AA; London Health Sciences Centre, 339 Windermere Rd, London N6A 3K7, ON, Canada; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Susan Huang SH; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Iyer H; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Johnson J; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Lotfy K; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Masellis M; LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada., Munoz DP; Centre for Neuroscience Studies, Queen's University, 18 Stuart St, Kingston, ON K7L 3N6, Canada., Rehman F; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Roshanov PS; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Swartz RH; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre and Department of Medicine (Neurology), University of Toronto, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada., Weir MA; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Hegele RA; Robarts Research Institute, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 3K7, Canada; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada., Connaughton DM; Department of Biochemistry, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada; Division of Medical Genetics, Department of Pediatrics, Victoria Hospital, London Health Science Center, 800 Commissioners Rd E, London, ON N6A 5W9, Canada; London Health Sciences Centre, 339 Windermere Rd, London N6A 3K7, ON, Canada; Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St, London, ON N6A 5C1, Canada. |
| المصدر: | Gene [Gene] 2024 Jun 27; Vol. 927, pp. 148731. Date of Electronic Publication: 2024 Jun 27. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier/North-Holland Country of Publication: Netherlands NLM ID: 7706761 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0038 (Electronic) Linking ISSN: 03781119 NLM ISO Abbreviation: Gene Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam, Elsevier/North-Holland, 1976- |
| مستخلص: | Vascular calcification is prevalent in chronic kidney disease (CKD). Genetic causes of CKD account for 10-20% of adult-onset disease. Vascular calcification is thought to be one of the most important risk factors for increased cardiovascular morbidity and mortality in CKD patients and is detectable in 80% of patients with end stage kidney disease (ESKD). Despite the high prevalence of vascular calcification in CKD, no single gene cause has been described. We hypothesized that variants in vascular calcification genes may contribute to disease pathogenesis in CKD, particularly in families who exhibit a predominant vascular calcification phenotype. We developed a list of eight genes that are hypothesized to play a role in vascular calcification due to their involvement in the ectopic calcification pathway: ABCC6, ALPL, ANK1, ENPP1, NT5E, SLC29A1, SLC20A2, and S100A12. With this, we assessed exome data from 77 CKD patients, who remained unsolved following evaluation for all known monogenic causes of CKD. We also analyzed an independent cohort (Ontario Neurodegenerative Disease Research Initiative (ONDRI), n = 520) who were screened for variants in ABCC6 and compared this to a control cohort of healthy adults (n = 52). We identified two CKD families with heterozygous pathogenic variants (R1141X and A667fs) in ABCC6. We identified 10 participants from the ONDRI cohort with heterozygous pathogenic or likely pathogenic variant in ABCC6. Replication in a healthy control cohort did not reveal any variants. Our study provides preliminary data supporting the hypothesis that ABCC6 may play a role in vascular calcification in CKD. By screening CKD patients for genetic causes early in the diagnostic pathway, patients with genetic causes associated with vascular calcification can potentially be preventatively treated with new therapeutics with aims to decrease mortality. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: ABCC6; Chronic kidney disease; ENPP1; Exome sequencing; Genetic kidney disease; Vascular calcification |
| تواريخ الأحداث: | Date Created: 20240629 Latest Revision: 20240705 |
| رمز التحديث: | 20240706 |
| DOI: | 10.1016/j.gene.2024.148731 |
| PMID: | 38944164 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0038 |
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| DOI: | 10.1016/j.gene.2024.148731 |