Analysis of HLA class II genes in Hashimoto's thyroiditis reveals differences compared to Graves' disease. 2008

A A Zeitlin, and J M Heward, and P R Newby, and J D Carr-Smith, and J A Franklyn, and S C L Gough, and M J Simmonds
Department of Medicine, Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) represent the commonest forms of autoimmune thyroid disease (AITD) each presenting with distinct clinical features. Progress has been made in determining association of HLA class II DRB1, DQB1 and DQA1 loci with GD demonstrating a predisposing effect for DR3 (DRB1(*)03-DQB1(*)02-DQA1(*)05) and a protective effect for DR7 (DRB1(*)07-DQB1(*)02-DQA1(*)02). Small data sets have hindered progress in determining HLA class II associations with HT. The aim of this study was to investigate DRB1-DQB1-DQA1 in the largest UK Caucasian HT case control cohort to date comprising 640 HT patients and 621 controls. A strong association between HT and DR4 (DRB1(*)04-DQB1(*)03-DQA1(*)03) was detected (P=6.79 x 10(-7), OR=1.98 (95% CI=1.51-2.59)); however, only borderline association of DR3 was found (P=0.050). Protective effects were also detected for DR13 (DRB1(*)13-DQB1(*)06-DQA1(*)01) (P=0.001, OR=0.61 (95% CI=0.45-0.83)) and DR7 (P=0.013, OR=0.70 (95% CI=0.53-0.93)). Analysis of our unique cohort of subjects with well characterized AITD has demonstrated clear differences in association within the HLA class II region between HT and GD. Although HT and GD share a number of common genetic markers this study supports the suggestion that differences in HLA class II genotype may, in part, contribute to the different immunopathological processes and clinical presentation of these related diseases.

UI MeSH Term Description Entries
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006111 Graves Disease A common form of hyperthyroidism with a diffuse hyperplastic GOITER. It is an autoimmune disorder that produces antibodies against the THYROID STIMULATING HORMONE RECEPTOR. These autoantibodies activate the TSH receptor, thereby stimulating the THYROID GLAND and hypersecretion of THYROID HORMONES. These autoantibodies can also affect the eyes (GRAVES OPHTHALMOPATHY) and the skin (Graves dermopathy). Basedow's Disease,Exophthalmic Goiter,Goiter, Exophthalmic,Graves' Disease,Basedow Disease,Hyperthyroidism, Autoimmune,Basedows Disease,Disease, Basedow,Disease, Basedow's,Disease, Graves,Disease, Graves',Exophthalmic Goiters,Goiters, Exophthalmic
D006113 United Kingdom Country in northwestern Europe including Great Britain and the northern one-sixth of the island of Ireland, located between the North Sea and north Atlantic Ocean. The capital is London. Great Britain,Isle of Man
D006239 Haplotypes The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. Haplotype
D006683 HLA-DQ Antigens A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases. HLA-DC Antigens,HLA-MB Antigens,HLA-DC,HLA-DQ,HLA-DS,HLA-DS Antigens,HLA-LB,HLA-LB Antigens,HLA-MB,Antigens, HLA-DC,Antigens, HLA-DQ,Antigens, HLA-DS,Antigens, HLA-LB,Antigens, HLA-MB,HLA DC Antigens,HLA DQ Antigens,HLA DS Antigens,HLA LB Antigens,HLA MB Antigens
D006684 HLA-DR Antigens A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS. HLA-DR,Antigens, HLA-DR,HLA DR Antigens
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D015331 Cohort Studies Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. Birth Cohort Studies,Birth Cohort Study,Closed Cohort Studies,Cohort Analysis,Concurrent Studies,Historical Cohort Studies,Incidence Studies,Analysis, Cohort,Cohort Studies, Closed,Cohort Studies, Historical,Studies, Closed Cohort,Studies, Concurrent,Studies, Historical Cohort,Analyses, Cohort,Closed Cohort Study,Cohort Analyses,Cohort Studies, Birth,Cohort Study,Cohort Study, Birth,Cohort Study, Closed,Cohort Study, Historical,Concurrent Study,Historical Cohort Study,Incidence Study,Studies, Birth Cohort,Studies, Cohort,Studies, Incidence,Study, Birth Cohort,Study, Closed Cohort,Study, Cohort,Study, Concurrent,Study, Historical Cohort,Study, Incidence
D015810 Linkage Disequilibrium Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. Disequilibrium, Linkage,Disequilibriums, Linkage,Linkage Disequilibriums

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