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Comprehensive human leukocyte antigen genotyping of patients with type 1 diabetes mellitus in Taiwan
Author(s) -
Tung YiChing,
Fann Cathy SJ,
Chang ChienChing,
Chu ChenChung,
Yang WeiShiung,
Hwu WuhLiang,
Chen PeiLung,
Tsai WenYu
Publication year - 2018
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.12645
Subject(s) - medicine , genotyping , immunology , diabetes mellitus , type 1 diabetes , antigen , human leukocyte antigen , virology , genotype , genetics , gene , endocrinology , biology
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.

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