Hla Antigens and Thyroid Autoantibodies in Patients With Graves' Disease and Their First Degree Relatives

Mather, B. A.; Roberts, D. F.; Scanlon, M. F.; Mukhtar, E. D.; Davies, Terry F.; Smith, B. R.; Hall, R.

doi:10.1111/j.1365-2265.1980.tb02130.x

Cited by 33 publications

(14 citation statements)

References 25 publications

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“…We did a multipoint linkage analysis, assuming homogeneity and heterogeneity, for the six chromosomes that showed evidence for linkage on the two-point LOD score analysis (chromosomes 2, 6,7,8,13,15). The marker positions on chromosomes and their distances were obtained from Genethon chromosomal genetic maps (http://www.genethon.fr).…”

Section: Multipoint Linkage Analysismentioning

confidence: 99%

“…Indeed, there is solid epidemiologic evidence for a genetic susceptibility to AITD including family studies demonstrating familial clustering of AITD (7,8), giving a sibling risk ratio of 16.9 (9) and a significantly higher concordance rate in monozygotic twins when compared with dizygotic twins (10,11). Genetic susceptibility to the production of thyroid antibodies was first suggested by Hall and Stanbury (12).…”

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confidence: 97%

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‘Linkage Analysis of Thyroid Antibody Production: Evidence for Shared Susceptibility to Clinical Autoimmune Thyroid Disease

Ban

Greenberg

Davies

et al. 2008

The Journal of Clinical Endocrinology &Amp; Metabolism

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We conclude that: 1) some of the genes/loci predisposing to TAb and AITD are shared, whereas distinct genes/loci also exist; (2) the presence of TAb in relatives of AITD patients may be associated with increased risk for the development of clinical AITD; and (3) further studies are needed to determine the predictive value of TAb levels for the development of clinical AITD in relatives of patients with familial AITD.

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Section: Multipoint Linkage Analysismentioning

confidence: 99%

mentioning

confidence: 97%

‘Linkage Analysis of Thyroid Antibody Production: Evidence for Shared Susceptibility to Clinical Autoimmune Thyroid Disease

Ban

Greenberg

Davies

et al. 2008

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…The pathogenesis of the AITDs involves a complex interaction between genetic and environmental factors. [2][3][4] Indeed, epidemiological evidence for a genetic predisposition to AITDs is exhibited by clustering in families, 5 giving a sibling risk ratio ( s ) of 15, 6 and a high concordance rate in monozygotic twins compared to dizygotic twins. 7 AITDs, by means of both association and linkage analyses.…”

Section: Introductionmentioning

confidence: 99%

A full genome screening in a large Tunisian family affected with thyroid autoimmune disorders

Maalej¹,

Makni²,

Ayadi

et al. 2001

Genes Immun

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The autoimmune thyroid diseases (AITDs) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are inherited as complex traits. We initiated a whole genome linkage study of patients with AITD, in order to identify the susceptibility genes involved in their pathogenesis. We studied 39 patients affected with GD or HT and 68 related controls, who belonged to a large consanguinous family composed of more than 200 members. Linkage analysis was performed using the lod score method under two arbitrary models, one dominant and one recessive. A positive lod score was found for D2S171, assuming a recessive mode of inheritance and 50% penetrance, which suggests the presence of a major AITD susceptibility gene on chromosome 2p21. However, no linkage was found with microsatellite markers spanning the HLA system. This locus localised outside MHC will be of interest for investigation of other autoimmune disorders. Genes and Immunity (2001) 2, 71-75.

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“…AITDs are complex diseases, which are caused by an interaction between susceptibility genes (6)(7)(8) and nongenetic factors, such as infection (9)(10)(11)(12). This paradigm is based on solid epidemiologic evidence demonstrating a genetic predisposition to AITDs, including: (i) familial clustering (13); (ii) a sibling risk ratio ( s ) of Ͼ10 (7,14); (iii) a high concordance rate in monozygotic twins when compared with dizygotic twins (15)(16)(17)(18); and (iv) the presence of thyroid autoantibodies, which are markers of subclinical AITD, in up to 50% of siblings of patients with AITD (19,20).…”

mentioning

confidence: 99%

Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease

Ban

Greenberg

Concepcion

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

173

131

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The 8q24 locus, which contains the thyroglobulin (Tg) gene, was previously shown to be strongly linked with autoimmune thyroid disease (AITD). We sequenced all 48 exons of the Tg gene and identified 14 single-nucleotide polymorphisms (SNPs). Case control association studies demonstrated that an exon 10 -12 SNP cluster and an exon 33 SNP were significantly associated with AITD (P < 0.01). Haplotype analysis demonstrated that the combination of these two SNP groups was more significantly associated with AITD (P < 0.001). Gene-gene interaction studies provided evidence for an interaction between HLA-DR3 and the exon 33 SNP, giving an odds ratio of 6.1 for Graves' disease. We then sequenced exons 10,12, and 33 of the mouse Tg gene in 19 strains of mice. Fifty percent of the strains susceptible to thyroiditis had a unique SNP haplotype at exons 10 and 12, whereas none of the mouse strains that were resistant to thyroiditis had this SNP haplotype (P ‫؍‬ 0.01). We concluded that Tg is a susceptibility gene for AITD, both in humans in and in mice. A combination of at least two Tg SNPs conferred susceptibility to human AITD. Moreover, the exon 33 SNP showed evidence for interaction with HLA-DR3 in conferring susceptibility to Graves' disease.Graves' disease ͉ Hashimoto's disease ͉ thyroiditis T he autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are among the most common human autoimmune diseases with recent data showing a prevalence of clinical AITD of up to 1% in the U.S. population (1, 2). The hallmark of GD is the production of thyroid-stimulating hormone receptor (TSHR)-stimulating antibodies causing hyperthyroidism, whereas HT is characterized by the apoptosis of thyrocytes, leading to hypothyroidism (reviewed in refs. 3 and 4). However, despite their contrasting clinical presentations, GD and HT share many features in common, mainly, infiltration of the thyroid by T cells and production of antithyroid autoantibodies [antithyroglobulin and anti-thyroid peroxidase (TPO) antibodies] (3-5). AITDs are complex diseases, which are caused by an interaction between susceptibility genes (6-8) and nongenetic factors, such as infection (9-12). This paradigm is based on solid epidemiologic evidence demonstrating a genetic predisposition to AITDs, including: (i) familial clustering (13); (ii) a sibling risk ratio ( s ) of Ͼ10 (7, 14); (iii) a high concordance rate in monozygotic twins when compared with dizygotic twins (15-18); and (iv) the presence of thyroid autoantibodies, which are markers of subclinical AITD, in up to 50% of siblings of patients with AITD (19,20).We have previously performed a whole-genome scan in a dataset of 102 multiplex, multigenerational AITD families (540 individuals; refs. 21-23). Three loci on chromosomes 6p, 8q, and 10q showed evidence for linkage with the entire AITD dataset giving maximum multipoint heterogeneity logarithm of odds (lod) scores of 2.0, 3.5, and 4.1, respectively. The 8q24 locus was also reported to be linked with AITD in a dat...

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Hla Antigens and Thyroid Autoantibodies in Patients With Graves' Disease and Their First Degree Relatives

Cited by 33 publications

References 25 publications

‘Linkage Analysis of Thyroid Antibody Production: Evidence for Shared Susceptibility to Clinical Autoimmune Thyroid Disease

‘Linkage Analysis of Thyroid Antibody Production: Evidence for Shared Susceptibility to Clinical Autoimmune Thyroid Disease

A full genome screening in a large Tunisian family affected with thyroid autoimmune disorders

Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease

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