Detection of Nonsynonymous Single Variants in Human HLA-DRB1 Exon 2 Associated with Renal Transplant Rejection.
Medicina (Kaunas)
; 59(6)2023 Jun 09.
Article
in En
| MEDLINE
| ID: mdl-37374320
Background: HLA-DRB1 is the most polymorphic gene in the human leukocyte antigen (HLA) class II, and exon 2 is critical because it encodes antigen-binding sites. This study aimed to detect functional or marker genetic variants of HLA-DRB1 exon 2 in renal transplant recipients (acceptance and rejection) using Sanger sequencing. Methods: This hospital-based case-control study collected samples from two hospitals over seven months. The 60 participants were equally divided into three groups: rejection, acceptance, and control. The target regions were amplified and sequenced by PCR and Sanger sequencing. Several bioinformatics tools have been used to assess the impact of non-synonymous single-nucleotide variants (nsSNVs) on protein function and structure. The sequences data that support the findings of this study with accession numbers (OQ747803-OQ747862) are available in National Center for Biotechnology Information (GenBank database). Results: Seven SNVs were identified, two of which were novel (chr6(GRCh38.p12): 32584356C>A (K41N) and 32584113C>A (R122R)). Three of the seven SNVs were non-synonymous and found in the rejection group (chr6(GRCh38.p12): 32584356C>A (K41N), 32584304A>G (Y59H), and 32584152T>A (R109S)). The nsSNVs had varying effects on protein function, structure, and physicochemical parameters and could play a role in renal transplant rejection. The chr6(GRCh38.p12):32584152T>A variant showed the greatest impact. This is because of its conserved nature, main domain location, and pathogenic effects on protein structure, function, and stability. Finally, no significant markers were identified in the acceptance samples. Conclusion: Pathogenic variants can affect intramolecular/intermolecular interactions of amino acid residues, protein function/structure, and disease risk. HLA typing based on functional SNVs could be a comprehensive, accurate, and low-cost method for covering all HLA genes while shedding light on previously unknown causes in many graft rejection cases.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Kidney Transplantation
Type of study:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Medicina (Kaunas)
Journal subject:
MEDICINA
Year:
2023
Document type:
Article
Affiliation country:
Sudan
Country of publication:
Switzerland