Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children.
HLA
HLA alleles and haplotypes
HLA association and disease
amino acid variations
type 1 diabetes
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
11
06
2023
accepted:
24
07
2023
medline:
29
8
2023
pubmed:
28
8
2023
entrez:
28
8
2023
Statut:
epublish
Résumé
Type 1 diabetes (T1D) is a complex autoimmune disorder that is highly prevalent globally. The interactions between genetic and environmental factors may trigger T1D in susceptible individuals. HLA genes play a significant role in T1D pathogenesis, and specific haplotypes are associated with an increased risk of developing the disease. Identifying risk haplotypes can greatly improve the genetic scoring for early diagnosis of T1D in difficult to rank subgroups. This study employed next-generation sequencing to evaluate the association between HLA class II alleles, haplotypes, and amino acids and T1D, by recruiting 95 children with T1D and 150 controls in the Kuwaiti population. Significant associations were identified for alleles at the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci, including DRB1*03:01:01, DQA1*05:01:01, and DQB1*02:01:01, which conferred high risk, and DRB1*11:04:01, DQA1*05:05:01, and DQB1*03:01:01, which were protective. The DRB1*03:01:01~DQA1*05:01:01~DQB1*02:01:01 haplotype was most strongly associated with the risk of developing T1D, while DRB1*11:04-DQA1*05:05-DQB1*03:01 was the only haplotype that rendered protection against T1D. We also identified 66 amino acid positions across the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes that were significantly associated with T1D, including novel associations. These results validate and extend our knowledge on the associations between HLA genes and T1D in Kuwaiti children. The identified risk alleles, haplotypes, and amino acid variations may influence disease development through effects on HLA structure and function and may allow early intervention via population-based screening efforts.
Identifiants
pubmed: 37638053
doi: 10.3389/fimmu.2023.1238269
pmc: PMC10457110
doi:
Substances chimiques
Amino Acids
0
HLA-DRB1 Chains
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1238269Informations de copyright
Copyright © 2023 Dashti, Nizam, Jacob, Al-Kandari, Al Ozairi, Thanaraj and Al-Mulla.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
J Clin Endocrinol Metab. 2005 Sep;90(9):5104-9
pubmed: 15985473
Diabetes. 2020 Jul;69(7):1573-1587
pubmed: 32245799
Nature. 1987 Oct 15-21;329(6140):599-604
pubmed: 3309680
Genes (Basel). 2021 Nov 25;12(12):
pubmed: 34946827
BMC Genomics. 2014 May 01;15:325
pubmed: 24884790
Diabetes. 1995 Jan;44(1):125-31
pubmed: 7813806
Diabetol Metab Syndr. 2022 Sep 12;14(1):128
pubmed: 36096955
Diabetes. 2013 Sep;62(9):3292-9
pubmed: 23801574
Diabetologia. 2005 Dec;48(12):2540-3
pubmed: 16320082
Clin Vaccine Immunol. 2009 Jan;16(1):136-8
pubmed: 19005023
Diabetes. 2020 Nov;69(11):2523-2535
pubmed: 32868339
HLA. 2018 Dec;92 Suppl 2:64-66
pubmed: 30488586
Exp Clin Endocrinol Diabetes. 2019 Oct;127(10):653-662
pubmed: 30428494
Clin Chem. 2011 Feb;57(2):176-85
pubmed: 21205883
BMJ. 1999 Mar 13;318(7185):698-702
pubmed: 10074012
Nat Genet. 2015 Aug;47(8):898-905
pubmed: 26168013
Clin Diagn Lab Immunol. 2004 Mar;11(2):292-6
pubmed: 15013978
Front Public Health. 2023 Jan 27;11:1014626
pubmed: 36778553
Front Genet. 2022 Mar 24;13:841879
pubmed: 35419034
Nucleic Acids Res. 2020 Jan 8;48(D1):D948-D955
pubmed: 31667505
Curr Genomics. 2007 Nov;8(7):453-65
pubmed: 19412418
PLoS One. 2018 Jun 20;13(6):e0198652
pubmed: 29924845
Hum Hered. 2000 Jul-Aug;50(4):242-6
pubmed: 10782017
Diabetes. 2013 Oct;62(10):3636-40
pubmed: 23835325
Dis Markers. 2019 Nov 20;2019:9786078
pubmed: 31827651
Sci Rep. 2020 Apr 20;10(1):6628
pubmed: 32313169
Diabetes Metab Res Rev. 2015 Mar;31(3):287-94
pubmed: 25256132
Diabetes. 2002 Jan;51(1):210-4
pubmed: 11756343
Transfus Apher Sci. 2013 Oct;49(2):200-4
pubmed: 23402837
Diabetes. 2019 Aug;68(8):1692-1704
pubmed: 31127057
Diabetes Care. 2006 Mar;29(3):662-7
pubmed: 16505523
Lancet Diabetes Endocrinol. 2022 Oct;10(10):741-760
pubmed: 36113507
Tissue Antigens. 1991 Mar;37(3):105-11
pubmed: 1908143
Sci Rep. 2021 Apr 23;11(1):8821
pubmed: 33893332
Genes Immun. 2008 Jun;9(4):358-63
pubmed: 18449200
N Engl J Med. 2014 Jul 3;371(1):42-9
pubmed: 24988556
Curr Diab Rep. 2011 Dec;11(6):533-42
pubmed: 21912932
Diabetes. 2018 Nov;67(11):2329-2336
pubmed: 30104249
EBioMedicine. 2021 Jul;69:103431
pubmed: 34153873
Hum Immunol. 2016 Mar;77(3):283-287
pubmed: 26708359
Clin Endocrinol (Oxf). 1991 May;34(5):383-6
pubmed: 1676351
Clin Genet. 1999 Dec;56(6):450-6
pubmed: 10665665
Pediatr Diabetes. 2016 Jul;17 Suppl 22:31-6
pubmed: 27411434
Curr Diabetes Rev. 2019;15(3):199-204
pubmed: 30058495
Genet Epidemiol. 1989;6(1):1-14
pubmed: 2659426
Proc Natl Acad Sci U S A. 1988 Nov;85(21):8111-5
pubmed: 3186714
Diabetes. 2002 Feb;51(2):545-51
pubmed: 11812768
Hum Mutat. 2017 Jul;38(7):788-797
pubmed: 28419628
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14074-9
pubmed: 16966600
PLoS One. 2018 Mar 1;13(3):e0193684
pubmed: 29494662
Pediatr Nephrol. 2022 Jan;37(1):79-93
pubmed: 33852054
Pediatr Diabetes. 2018 May;19(3):346-353
pubmed: 29094512
Pediatr Diabetes. 2017 Dec;18(8):761-766
pubmed: 27981709
Sultan Qaboos Univ Med J. 2023 Feb;23(1):68-75
pubmed: 36865417
Diabetologia. 2015 May;58(5):980-7
pubmed: 25660258
PLoS One. 2008 Jan 02;3(1):e1374
pubmed: 18167535
J Autoimmun. 2015 Nov;64:101-12
pubmed: 26272854
Diabetes Metab Res Rev. 2020 Nov;36(8):e3345
pubmed: 32418312
Diabetes. 2008 Apr;57(4):1084-92
pubmed: 18252895