HLA alleles, especially amino-acid signatures of HLA-DPB1, might contribute to the molecular pathogenesis of early-onset autoimmune thyroid disease

Autor: Min Ho Jung, In-Cheol Baek, Tai-Gyu Kim, Moonbae Ahn, Hyung J. Kim, Dong-Hwan Shin, Won Kyoung Cho, Eun-Jeong Choi, Byung Kyu Suh
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Heredity
Graves' disease
Gene Expression
Artificial Gene Amplification and Extension
Polymerase Chain Reaction
Database and Informatics Methods
0302 clinical medicine
Gene Frequency
Medicine and Health Sciences
Age of Onset
Child
HLA-DP beta-Chains
Thyroid
Multidisciplinary
biology
Graves Disease
Genetic Mapping
medicine.anatomical_structure
Child
Preschool
030220 oncology & carcinogenesis
Amino Acid Analysis
Medicine
Female
Anatomy
Sequence Analysis
Research Article
Adult
Adolescent
Hashimoto's disease
Bioinformatics
Science
Immunology
Endocrine System
Hashimoto Disease
Human leukocyte antigen
Research and Analysis Methods
Major histocompatibility complex
Autoimmune Diseases
03 medical and health sciences
Amino Acid Sequence Analysis
Genetics
medicine
Humans
Genetic Predisposition to Disease
Allele
Molecular Biology Techniques
Molecular Biology
Alleles
Molecular Biology Assays and Analysis Techniques
Polymorphism
Genetic
Hashimoto's Disease
HLA-DPB1
Haplotype
Biology and Life Sciences
medicine.disease
030104 developmental biology
Haplotypes
Genetic Loci
Graves' Disease
Case-Control Studies
biology.protein
Clinical Immunology
Clinical Medicine
Zdroj: PLoS ONE, Vol 14, Iss 5, p e0216941 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: The major histocompatibility complex region has been suggested to play an important role in the development of autoimmune thyroid disease (AITD). In this study, we investigated the associations of human leukocyte antigen (HLA) alleles and amino acid variants of HLA with early-onset AITD. HLA class I and class II genes were analyzed in 116 Korean children with AITDs (Graves' disease [GD]: 71, Hashimoto's disease [HD]: 45) and 142 healthy controls. HLA-B*46:01 (OR = 3.96, Pc = 0.008), -C*01:02 (OR = 2.51 Pc = 0.04), -DPB1*02:02 (OR = 3.99, Pc = 0.04), and -DPB1*05:01 (OR = 4.6, Pc = 0.003) were significantly associated with GD, and HLA-A*02:07 (OR = 4.68, Pc = 0.045) and -DPB1*02:02 (OR = 6.57, Pc = 0.0001) with HD. The frequency of HLA-DPB1*05:01 was significantly higher in GD patients than in HD patients (Pc = 0.0005). Furthermore, differences were found between patients with Thyroid associated ophthalmopathy (TAO) and those without TAO in the distribution of HLA-B*54:01 (8.6% vs. 30.6%, P = 0.04) and -C*03:03 (37.1% vs. 11.1%, P = 0.02). In the analysis of amino acid variants of HLA molecules, both Leu35 (OR = 23.38, P = 0.0002) and Glu55 (OR = 23.38, P = 0.0002) of HLA-DPB1 were strongly associated with GD and showed different distributions between GD and HD (P = 0.001). Our results suggest that HLA alleles, especially amino-acid signatures of the HLA-DP β chain, might contribute to the molecular pathogenesis of early-onset AITD.
Databáze: OpenAIRE
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