PMID- 37374320
OWN - NLM
STAT- MEDLINE
DCOM- 20230629
LR  - 20230701
IS  - 1648-9144 (Electronic)
IS  - 1010-660X (Print)
IS  - 1010-660X (Linking)
VI  - 59
IP  - 6
DP  - 2023 Jun 9
TI  - Detection of Nonsynonymous Single Variants in Human HLA-DRB1 Exon 2 Associated 
      with Renal Transplant Rejection.
LID - 10.3390/medicina59061116 [doi]
LID - 1116
AB  - 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.
FAU - Hassan, Mohamed M
AU  - Hassan MM
AUID- ORCID: 0000-0003-1544-7932
AD  - Department of Hematology, Faculty of Medical Laboratory Sciences, National 
      University, Khartoum 11111, Sudan.
FAU - Hussain, Mohamed A
AU  - Hussain MA
AUID- ORCID: 0000-0003-1487-2005
AD  - Department of Pharmaceutical Microbiology, Faculty of Pharmacy, International 
      University of Africa, Khartoum 11111, Sudan.
FAU - Ali, Sababil S
AU  - Ali SS
AD  - Department of Parasitology and Medical Entomology, Faculty of Medical Laboratory 
      Sciences, National University, Khartoum11111, Sudan.
FAU - Mahdi, Mohammed A
AU  - Mahdi MA
AUID- ORCID: 0000-0002-6728-3899
AD  - Department of Chemical Pathology, Faculty of Medical Laboratory Sciences, 
      National University, Khartoum 11111, Sudan.
FAU - Mohamed, Nouh Saad
AU  - Mohamed NS
AUID- ORCID: 0000-0001-6843-3361
AD  - Molecular Biology Unit, Sirius Training and Research Centre, Khartoum 11111, 
      Sudan.
FAU - AbdElbagi, Hanadi
AU  - AbdElbagi H
AD  - Molecular Biology Unit, Sirius Training and Research Centre, Khartoum 11111, 
      Sudan.
FAU - Mohamed, Osama
AU  - Mohamed O
AUID- ORCID: 0000-0002-5338-6643
AD  - Department of Molecular Biology, National University Biomedical Research 
      Institute, National University, Khartoum 11111, Sudan.
FAU - Sherif, Asmaa E
AU  - Sherif AE
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz 
      University, Al-kharj 11942, Saudi Arabia.
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 
      35516, Egypt.
FAU - Osman, Wadah
AU  - Osman W
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz 
      University, Al-kharj 11942, Saudi Arabia.
AD  - Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Al-Qasr 
      Ave, Khartoum 11111, Sudan.
FAU - Ibrahim, Sabrin R M
AU  - Ibrahim SRM
AUID- ORCID: 0000-0002-6858-7560
AD  - Preparatory Year Program, Department of Chemistry, Batterjee Medical College, 
      Jeddah 21442, Saudi Arabia.
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 
      71526, Egypt.
FAU - Ghazawi, Kholoud F
AU  - Ghazawi KF
AD  - Clinical Pharmacy Department, College of Pharmacy, Umm Al-Qura University, Makkah 
      24382, Saudi Arabia.
FAU - Miski, Samar F
AU  - Miski SF
AD  - Department of Pharmacology and Toxicology, College of Pharmacy, Taibah 
      University, Al-Madinah Al-Munawwarah 30078, Saudi Arabia.
FAU - Mohamed, Gamal A
AU  - Mohamed GA
AUID- ORCID: 0000-0002-2971-6008
AD  - Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, 
      King Abdulaziz University, Jeddah 21589, Saudi Arabia.
FAU - Ashour, Ahmed
AU  - Ashour A
AUID- ORCID: 0000-0003-4081-0369
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz 
      University, Al-kharj 11942, Saudi Arabia.
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 
      35516, Egypt.
LA  - eng
GR  - PSAU/2023/R/1444/This study is supported via funding from Prince Sattam bin 
      Abdulaziz University. Project number (PSAU/2023/R/1444)./
PT  - Journal Article
DEP - 20230609
PL  - Switzerland
TA  - Medicina (Kaunas)
JT  - Medicina (Kaunas, Lithuania)
JID - 9425208
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Humans
MH  - HLA-DRB1 Chains/genetics
MH  - *Kidney Transplantation/adverse effects
MH  - Case-Control Studies
MH  - HLA Antigens
MH  - Graft Rejection/genetics
MH  - Exons/genetics
MH  - Alleles
PMC - PMC10305364
OTO - NOTNLM
OT  - DNA sequencing
OT  - HLA typing
OT  - HLA-DRB1 gene
OT  - graft rejection
OT  - health and wellbeing
OT  - renal diseases
OT  - single nucleotide variants snvs
COIS- The authors declare no conflict of interest.
EDAT- 2023/06/28 06:42
MHDA- 2023/06/29 06:43
PMCR- 2023/06/09
CRDT- 2023/06/28 01:25
PHST- 2023/04/14 00:00 [received]
PHST- 2023/06/01 00:00 [revised]
PHST- 2023/06/06 00:00 [accepted]
PHST- 2023/06/29 06:43 [medline]
PHST- 2023/06/28 06:42 [pubmed]
PHST- 2023/06/28 01:25 [entrez]
PHST- 2023/06/09 00:00 [pmc-release]
AID - medicina59061116 [pii]
AID - medicina-59-01116 [pii]
AID - 10.3390/medicina59061116 [doi]
PST - epublish
SO  - Medicina (Kaunas). 2023 Jun 9;59(6):1116. doi: 10.3390/medicina59061116.