دورية أكاديمية
أعرض في EDS

Polygenic risk score for acute rejection based on donor-recipient non-HLA genotype mismatch.

التفاصيل البيبلوغرافية
العنوان: Polygenic risk score for acute rejection based on donor-recipient non-HLA genotype mismatch.
المؤلفون: Cao R; Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America., Schladt DP; Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States of America., Dorr C; Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States of America.; Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America., Matas AJ; Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America., Oetting WS; Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, United States of America., Jacobson PA; Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, United States of America., Israni A; Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States of America.; Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America., Chen J; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Guan W; Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
المصدر: PloS one [PLoS One] 2024 May 31; Vol. 19 (5), pp. e0303446. Date of Electronic Publication: 2024 May 31 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Polymorphism, Single Nucleotide* , Kidney Transplantation* , Graft Rejection*/genetics , Graft Rejection*/immunology , Genome-Wide Association Study* , Genotype*, Humans ; Female ; Male ; Middle Aged ; Adult ; HLA Antigens/genetics ; Multifactorial Inheritance ; Risk Factors ; Living Donors ; Cohort Studies ; Genetic Risk Score
مستخلص: Background: Acute rejection (AR) after kidney transplantation is an important allograft complication. To reduce the risk of post-transplant AR, determination of kidney transplant donor-recipient mismatching focuses on blood type and human leukocyte antigens (HLA), while it remains unclear whether non-HLA genetic mismatching is related to post-transplant complications.
Methods: We carried out a genome-wide scan (HLA and non-HLA regions) on AR with a large kidney transplant cohort of 784 living donor-recipient pairs of European ancestry. An AR polygenic risk score (PRS) was constructed with the non-HLA single nucleotide polymorphisms (SNPs) filtered by independence (r2 < 0.2) and P-value (< 1×10-3) criteria. The PRS was validated in an independent cohort of 352 living donor-recipient pairs.
Results: By the genome-wide scan, we identified one significant SNP rs6749137 with HR = 2.49 and P-value = 2.15×10-8. 1,307 non-HLA PRS SNPs passed the clumping plus thresholding and the PRS exhibited significant association with the AR in the validation cohort (HR = 1.54, 95% CI = (1.07, 2.22), p = 0.019). Further pathway analysis attributed the PRS genes into 13 categories, and the over-representation test identified 42 significant biological processes, the most significant of which is the cell morphogenesis (GO:0000902), with 4.08 fold of the percentage from homo species reference and FDR-adjusted P-value = 8.6×10-4.
Conclusions: Our results show the importance of donor-recipient mismatching in non-HLA regions. Additional work will be needed to understand the role of SNPs included in the PRS and to further improve donor-recipient genetic matching algorithms. Trial registry: Deterioration of Kidney Allograft Function Genomics (NCT00270712) and Genomics of Kidney Transplantation (NCT01714440) are registered on ClinicalTrials.gov.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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معلومات مُعتمدة: U01 AI058013 United States AI NIAID NIH HHS; U19 AI070119 United States AI NIAID NIH HHS
سلسلة جزيئية: ClinicalTrials.gov NCT01714440
المشرفين على المادة: 0 (HLA Antigens)
تواريخ الأحداث: Date Created: 20240531 Date Completed: 20240531 Latest Revision: 20240603
رمز التحديث: 20240603
مُعرف محوري في PubMed: PMC11142483
DOI: 10.1371/journal.pone.0303446
PMID: 38820342
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0303446