Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children.

Autor: Dashti M; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait., Nizam R; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait., Jacob S; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait., Al-Kandari H; Department of Population Health, Dasman Diabetes Institute, Dasman, Kuwait.; Department of Pediatrics, Farwaniya Hospital, Ministry of Health, Sabah Al Nasser, Kuwait., Al Ozairi E; Clinical Care Research and Trials, Dasman Diabetes Institute, Dasman, Kuwait.; Faculty of Medicine, Kuwait University, Jabriya, Kuwait., Thanaraj TA; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait., Al-Mulla F; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman, Kuwait.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2023 Aug 10; Vol. 14, pp. 1238269. Date of Electronic Publication: 2023 Aug 10 (Print Publication: 2023).
DOI: 10.3389/fimmu.2023.1238269
Abstrakt: 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.
Competing Interests: 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.
(Copyright © 2023 Dashti, Nizam, Jacob, Al-Kandari, Al Ozairi, Thanaraj and Al-Mulla.)
Databáze: MEDLINE
Externí odkaz: