Comprehensive human leukocyte antigen genotyping of patients with type 1 diabetes mellitus in Taiwan
Journal
Pediatric Diabetes
Journal Volume
19
Journal Issue
4
Pages
699-706
Date Issued
2018
Author(s)
Fann C.S.-J.
Chang C.-C.
Chu C.-C.
Tsai W.-Y.
Abstract
Background: Type 1 diabetes (T1D) mellitus is an autoimmune disorder involving both complex genetic and environmental factors. The incidence rates are low in Asian countries, and the specific, explanatory genetic factors underlying this have been investigated. The aim of this study was to elucidate the association of human leukocyte antigen (HLA) alleles/haplotypes with T1D in Taiwan. Methods: We performed direct comprehensive genotyping of 6 classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1) to 4-digit resolution in 104 unrelated T1D patients and 504 controls. Twenty-four of the 104 patients also exhibited thyroid autoimmunity. Results: Three major susceptibility haplotypes were identified: DRB1*03:01-DQB1*02:01 (odds ratio [OR] = 5.39 under the dominant model, P = 2.3 × 10?13), DRB1*04:05-DQB1*04:01 (OR = 2.44, P = 5.0 × 10?4), and DRB1*09:01-DQB1*03:03 (OR = 2.02, P = 1.4 × 10?3); one protective haplotype was identified: DRB1*08:03-DQB1*06:01 (OR = 0.10, P = 1.6 × 10?3). DRB1*03:01-DQB1*02:01, the major T1D susceptibility haplotype, was found at a lower frequency in T1D patients with thyroid autoimmunity. The T1D protective allele DRB1*12:02 was shown to be protective against Graves’ disease in our previous report. Conclusion: In addition to clarifying the roles of several known T1D HLA alleles and haplotypes, we discovered that the DRB1*08:03-DQB1*06:01 haplotype is protective against T1D. The DRB1*12:02 allele protected against both T1D and Graves’ disease. ? 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Other Subjects
HLA A antigen; HLA antigen; HLA B antigen; HLA C antigen; HLA DPB1 antigen; HLA DQB1 antigen; HLA DRB1 antigen; HLA antigen; adult; allele; Article; autoimmune thyroiditis; child; controlled study; diabetic patient; female; gene frequency; gene identification; gene locus; genetic association; genetic model; genetic susceptibility; genotype; Graves disease; haplotype; HLA A gene; HLA B gene; HLA C gene; HLA DPB1 gene; HLA DQB1 gene; HLA DRB1 gene; HLA gene; human; insulin dependent diabetes mellitus; major clinical study; male; priority journal; school child; Taiwan; adolescent; autoimmune thyroiditis; case control study; genetic association study; genetic predisposition; genetics; genotype; genotyping technique; Graves disease; histocompatibility test; insulin dependent diabetes mellitus; preschool child; procedures; Adolescent; Case-Control Studies; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Genotyping Techniques; Graves Disease; Histocompatibility Testing; HLA Antigens; Humans; Male; Taiwan; Thyroiditis, Autoimmune
Publisher
Blackwell Publishing Ltd
Type
journal article