Unravelling the genetic complexity of autoimmune thyroid disease: HLA, CTLA-4 and beyond

Simmonds, M. J. and Gough, S. C. L. (2004) Unravelling the genetic complexity of autoimmune thyroid disease: HLA, CTLA-4 and beyond. Clinical and Experimental Immunology, 136 (1). pp. 1-10. ISSN 0009-9104

Full content URL: http://dx.doi.org/10.1111/j.1365-2249.2004.02424.x

2004 Clin Exp Immunol Graves' disease Review.pdf
2004 Clin Exp Immunol Graves' disease Review.pdf - Whole Document

Item Type:Review
Item Status:Live Archive


The autoimmune thyroid diseases (AITDs) including Graves' disease (GD) and autoimmune hypothyroidism (AIH) are the commonest of the autoimmune conditions affecting 2-5 of the western population. Twin studies have clearly demonstrated that AITDs are caused by a combination of both environmental and genetic factors. Association of the HLA class II region with AITD has been documented for over 20 years now, but the primary aetiological variant in this region remains unknown. More recently the CTLA-4 gene region has been identified as the second locus conferring susceptibility to AITD. In contrast to HLA, a polymorphism of the CTLA-4 gene, which encodes an important negative regulator of the immune system, has been identified as a candidate for a primary determinant for AITD. A large number of candidate gene and genome wide linkage studies have been involved in the search for the elusive 'third' locus. The thyroglobulin (Tg) gene in humans maps to chromosome 8q, which has been linked in family studies to AITD. A number of association studies in humans and the mouse model for AITD are beginning to implicate the Tg gene although convincing evidence for a primary causative role is still needed. The establishment of large DNA disease resources along with more detailed genetic maps and the development of faster, more effective, high throughput genotyping and sequencing methods, provides some sense of optimism that novel loci will be identified in the near future and the complex aetiology of AITD will be further unraveled.

Keywords:cytotoxic T lymphocyte antigen 4, HLA antigen, thyroglobulin, chromosome 8q, disease model, DNA determination, environmental factor, gene locus, gene mapping, gene sequence, genetic association, genetic linkage, genotype, Graves disease, Hashimoto disease, heredity, HLA system, human, hypothyroidism, population risk, priority journal, review, Tg gene, thyroid disease, Animals, Antigens, CD, Antigens, CD28, Antigens, Differentiation, Autoimmune Diseases, Genetic Predisposition to Disease, Humans, Major Histocompatibility Complex, Mice, Thyroid Diseases
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:22637
Deposited On:17 Mar 2016 21:39

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