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Article ; Online: Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progression.

Yesmin, Kadija / Hargreaves, Chantal / Newby, Paul R / Brand, Oliver J / Heward, Joanne M / Franklyn, Jayne A / Gough, Stephen C L / Simmonds, Matthew J

Clinical endocrinology

2010 Volume 73, Issue 1, Page(s) 119–125

Abstract: Objective: Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is ... ...

Abstract	Objective: Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves' disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region. Design: A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region. Patients: A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort. Measurements: We used the chi(2)-test to investigate association between the Tag SNPs and GD. Results: Association between the rs1801274 (P = 0.003, OR = 1.12 [95% CI = 1.03-1.22] and rs6427598 (P = 0.012, OR = 0.90 [95% CI = 0.83-0.98]) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes. Conclusions: This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general.
MeSH term(s)	Autoantibodies/metabolism ; Case-Control Studies ; Disease Progression ; Genetic Predisposition to Disease ; Graves Disease/genetics ; Graves Disease/immunology ; Humans ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, IgG/genetics
Chemical Substances	Autoantibodies ; Fc gamma receptor IIA ; Receptors, IgG
Language	English
Publishing date	2010-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121745-8
ISSN	1365-2265 ; 0300-0664
ISSN (online)	1365-2265
ISSN	0300-0664
DOI	10.1111/j.1365-2265.2010.03780.x
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Article: A novel and major association of HLA-C in Graves' disease that eclipses the classical HLA-DRB1 effect.

Simmonds, Matthew J / Howson, Joanna M M / Heward, Joanne M / Carr-Smith, Jackie / Franklyn, Jayne A / Todd, John A / Gough, Stephen C L

Human molecular genetics

2007 Volume 16, Issue 18, Page(s) 2149–2153

Abstract: Association of the major histocompatibility complex (MHC) class II-encoded HLA-DRB1-DQA1-DQB1 haplotype with Graves' disease (GD) has been known for several years. Recent evidence from other autoimmune diseases has suggested that the HLA class I encoded ... ...

Abstract	Association of the major histocompatibility complex (MHC) class II-encoded HLA-DRB1-DQA1-DQB1 haplotype with Graves' disease (GD) has been known for several years. Recent evidence from other autoimmune diseases has suggested that the HLA class I encoded HLA-B/-C molecules could be conferring HLA-DRB1-DQA1-DQB1 independent effects on disease. The aim of this study was to determine the effect of HLA-B and HLA-C in GD in a white ethnic group of 806 patients with GD and 487 control subjects from the UK. Of the five loci (HLA-B, -C, -DRB1, -DQA1, -DQB1), HLA-C demonstrated the strongest association (P = 1.20 x 10(-20)) with HLA-C07 predisposing [OR = 1.63, 95% CI (1.23-2.17)] and both HLA-C03 [OR = 0.54, 95% CI (0.38-0.77)], HLA-C*16 [OR = 0.36, 95% CI (0.21-0.61)] protective. The other loci were then tested for HLA-C-independent associations. HLA-B was found to be associated independently of HLA-C (P = 1.54 x 10(-6)) with the other three loci, HLA-DRB1, HLA-DQB1 and HLA-DQA1, also improving the model but with less confidence (P > 10(-5)). This study has for the first time provided evidence of a primary association of HLA-C, and to a lesser extent HLA-B, with GD. Class II loci could still have effects on GD, but they appear smaller than the HLA-C association. A full investigation of the MHC region, including all class I and II loci is now required. Our results point to a primary role for class I-mediated responses in GD, a condition classically assumed to be a straightforward HLA-class II-restricted autoantibody response to the thyroid stimulating hormone receptor.
MeSH term(s)	Autoantibodies/genetics ; Autoantibodies/immunology ; European Continental Ancestry Group ; Female ; Graves Disease/genetics ; Graves Disease/immunology ; HLA-B Antigens/genetics ; HLA-B Antigens/immunology ; HLA-C Antigens/genetics ; HLA-C Antigens/immunology ; HLA-DR Antigens/genetics ; HLA-DR Antigens/immunology ; HLA-DRB1 Chains ; Humans ; Male ; Quantitative Trait Loci/genetics ; Quantitative Trait Loci/immunology ; Receptors, Thyrotropin/genetics ; Receptors, Thyrotropin/immunology
Chemical Substances	Autoantibodies ; HLA-B Antigens ; HLA-C Antigens ; HLA-DR Antigens ; HLA-DRB1 Chains ; Receptors, Thyrotropin
Language	English
Publishing date	2007-09-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddm165
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Zs.A 3469: Show issues

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Article: Association of PTPN22 haplotypes with Graves' disease.

Heward, Joanne M / Brand, Oliver J / Barrett, Jeffrey C / Carr-Smith, Jackie D / Franklyn, Jayne A / Gough, Stephen C

The Journal of clinical endocrinology and metabolism

2007 Volume 92, Issue 2, Page(s) 685–690

Abstract: Context: A recent study reported associations of a series of single nucleotide polymorphisms (SNPs) within PTPN22, including rs2476601, with rheumatoid arthritis.: Objective: Having previously reported significant association of the T allele of ... ...

Abstract	Context: A recent study reported associations of a series of single nucleotide polymorphisms (SNPs) within PTPN22, including rs2476601, with rheumatoid arthritis. Objective: Having previously reported significant association of the T allele of rs2476601 in a Graves' disease (GD) cohort, we sought to determine whether novel rheumatoid arthritis-associated SNPs were also contributing to susceptibility to GD. Design: Case control and family-based studies of five PTPN22 tag SNPs were performed. Setting: An United Kingdom academic department of medicine was the setting for the study. Patients or other participants: A total of 768 GD patients, 768 control subjects, and 313 families with autoimmune thyroid disease participated. Main outcome measure: Tests for association with disease were the main outcome measure. Results: No association with disease of any of the individual SNPs and no correlation between genotype and clinical phenotype were seen. However, haplotype analysis of the SNP markers with addition of rs2476601 did reveal a strong association of a haplotype containing the T allele, in both the case control (chi2 = 29.13; P = 6.77 x 10(-8)) and family data sets (chi2 = 5.24; P = 0.02). Furthermore, a novel protective effect of a haplotype containing all six SNPs was observed (chi2 = 17.02; P = 3.7 x 10(-5)). Conclusions: These data suggest that the association of SNPs within the PTPN22 region differs between autoimmune diseases, occurring individually and/or as part of a haplotype, indicating that the mechanisms by which PTPN22 confers susceptibility to GD may, in part, be disease specific.
MeSH term(s)	Arthritis, Rheumatoid/genetics ; Case-Control Studies ; Cimicifuga ; Family Health ; Gene Frequency ; Genetic Predisposition to Disease ; Graves Disease/genetics ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; Protein Tyrosine Phosphatase, Non-Receptor Type 22 ; Protein Tyrosine Phosphatases/genetics
Chemical Substances	PTPN22 protein, human (EC 3.1.3.48) ; Protein Tyrosine Phosphatase, Non-Receptor Type 22 (EC 3.1.3.48) ; Protein Tyrosine Phosphatases (EC 3.1.3.48)
Language	English
Publishing date	2007-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2006-2064
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Article: Association of the interleukin-2 receptor alpha (IL-2Ralpha)/CD25 gene region with Graves' disease using a multilocus test and tag SNPs.

Brand, Oliver J / Lowe, Christopher E / Heward, Joanne M / Franklyn, Jayne A / Cooper, Jason D / Todd, John A / Gough, Stephen C L

Clinical endocrinology

2007 Volume 66, Issue 4, Page(s) 508–512

Abstract: Objective: A small number of immune response genes have been consistently associated with the common autoimmune conditions. Recently, a linkage disequilibrium (LD) mapping approach, using tag single nucleotide polymorphisms (SNPs), identified genetic ... ...

Abstract	Objective: A small number of immune response genes have been consistently associated with the common autoimmune conditions. Recently, a linkage disequilibrium (LD) mapping approach, using tag single nucleotide polymorphisms (SNPs), identified genetic association between type 1 diabetes (T1D) and the interleukin-2 receptor alpha (IL-2Ralpha)/CD25 gene region on chromosome 10p15. Because certain autoimmune diseases, such as autoimmune thyroid disease (AITD) and T1D cluster together in certain families, we sought to determine if the TID-associated CD25 region was also associated with Graves' disease (GD). Design: We performed a case-control association study of 20 tag SNPs. Patients: 1896 GD patients were collected from seven major centres in the UK and 1822 geographically matched controls from the 1958 British Birth Cohort. Measurements: The 20 tag SNPs were analysed using a multilocus test to identify an association between GD and the CD25 region. Odds ratios (ORs) were calculated for the tag SNPs, allowing a comparison with previous results for T1D. RESULTS The multilocus test provided statistical evidence of an association between GD and the CD25 region (P = 4.5 x 10(-4)), with the pattern of association of the 20 tag SNPs similar to that found in T1D. CONCLUSIONS Association with GD, as well as that previously reported with T1D, suggests that the CD25 region is acting as a general susceptibility locus for autoimmune disease, and is consistent with a major role for the IL-2-receptor pathway in the development and function of T cells in the control of autoimmunity.
MeSH term(s)	Case-Control Studies ; Diabetes Mellitus, Type 1/genetics ; Female ; Gene Frequency ; Genetic Markers ; Genetic Predisposition to Disease ; Genotype ; Graves Disease/genetics ; Health Surveys ; Humans ; Interleukin-2 Receptor alpha Subunit/genetics ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; Sequence Tagged Sites ; United Kingdom
Chemical Substances	Genetic Markers ; Interleukin-2 Receptor alpha Subunit
Language	English
Publishing date	2007-03-16
Publishing country	England
Document type	Journal Article ; Multicenter Study
ZDB-ID	121745-8
ISSN	1365-2265 ; 0300-0664
ISSN (online)	1365-2265
ISSN	0300-0664
DOI	10.1111/j.1365-2265.2007.02762.x
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Article: Polymorphism of the CTLA-4 gene is associated with autoimmune hypothyroidism in the United Kingdom.

Nithiyananthan, Ratnasingam / Heward, Joanne M / Allahabadia, Amit / Franklyn, Jayne A / Gough, Stephen C L

Thyroid : official journal of the American Thyroid Association

2002 Volume 12, Issue 1, Page(s) 3–6

Abstract: The cytotoxic T-lymphocyte-associated-4 (CTLA-4) molecule plays an important role in immune regulation by downregulating activation of T cells by antigen-presenting cells. Polymorphisms of the CTLA-4 gene have been shown to be associated with ... ...

Abstract	The cytotoxic T-lymphocyte-associated-4 (CTLA-4) molecule plays an important role in immune regulation by downregulating activation of T cells by antigen-presenting cells. Polymorphisms of the CTLA-4 gene have been shown to be associated with susceptibility to a number of autoimmune diseases. Some, but not all, studies suggest association between the CTLA-4 gene and autoimmune hypothyroidism. The aim of this study was to determine whether allelic association was present between the A-G single nucleotide polymorphism (SNP) at position 49 in exon 1 of the CTLA-4 gene and autoimmune hypothyroidism. The study was performed in 158 patients with autoimmune hypothyroidism and 384 control subjects. All subjects were white Caucasians from the United Kingdom. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using the restriction enzyme Bbv1. There was a significant excess of the G allele in patients with autoimmune hypothyroidism compared with controls (43% vs. 32% respectively; chi2 = 10.7, p = 0.001; odds ratio 1.57). The GG and the AG genotypes were found to be more frequent in patients with autoimmune hypothyroidism than controls (17% vs. 8.8% and 50% vs. 46% respectively; chi2 = 11.7, p = 0.003). These results suggest that the CTLA-4 gene region on chromosome 2q33 is a susceptibility locus for autoimmune hypothyroidism in the United Kingdom.
MeSH term(s)	Abatacept ; Antigens, CD ; Antigens, Differentiation/genetics ; Autoimmune Diseases/genetics ; CTLA-4 Antigen ; Chromosomes, Human, Pair 2 ; Exons ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypothyroidism/immunology ; Immunoconjugates ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; United Kingdom
Chemical Substances	Antigens, CD ; Antigens, Differentiation ; CTLA-4 Antigen ; CTLA4 protein, human ; Immunoconjugates ; Abatacept (7D0YB67S97)
Language	English
Publishing date	2002-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1086044-7
ISSN	1557-9077 ; 1050-7256
ISSN (online)	1557-9077
ISSN	1050-7256
DOI	10.1089/105072502753451896
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Zs.A 3307: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Polymorphisms of interleukin 4 receptor gene and interleukin 10 gene are not associated with Graves' disease in the UK.

Tait, Karen F / Nithiyananthan, Ratnasingam / Heward, Joanne M / Barnett, Anthony H / Franklyn, Jayne A / Gough, Stephen C L

Autoimmunity

2004 Volume 37, Issue 3, Page(s) 189–194

Abstract: Graves' disease (GD) is an autoimmune disorder of the thyroid gland and both environmental and genetic factors contribute to disease aetiology. Cytokines, such as interleukin 4 (IL-4) and interleukin 10 (IL-10), are involved in the immune response and ... ...

Abstract	Graves' disease (GD) is an autoimmune disorder of the thyroid gland and both environmental and genetic factors contribute to disease aetiology. Cytokines, such as interleukin 4 (IL-4) and interleukin 10 (IL-10), are involved in the immune response and may be implicated in the autoimmune disease process. Associations have been reported between single nucleotide polymorphisms (SNPs) of IL-10 and the Ile50Val polymorphism of the IL-4 receptor gene (IL-4R) gene and atopy and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The autoimmune diseases cluster within families and susceptibility genes may overlap between the different disorders. Therefore, we investigated 5 SNPs (-592C/A, -657G/A, - 819C/T, -1349A/G, and -2013G/A) in the promoter region of the IL-10 and the Ile50Val polymorphism (A/G) in the IL-4R in a large UK population based case-control dataset with GD. No association was found between the polymorphisms studied and GD and no significant differences were found in genotype or allele frequencies between the patients and control subjects. We conclude these polymorphisms of IL-10 and IL-4R previously associated with other immune mediated diseases, do not confer susceptibility to GD in white Caucasians in the United Kingdom.
MeSH term(s)	Genetic Predisposition to Disease ; Graves Disease/genetics ; Humans ; Interleukin-10/genetics ; Polymorphism, Single Nucleotide/genetics ; Receptors, Interleukin-4/genetics ; United Kingdom
Chemical Substances	Receptors, Interleukin-4 ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2004-09-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1025450-x
ISSN	0891-6934
ISSN	0891-6934
DOI	10.1080/08916930410001666631
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Zs.A 2777: Show issues

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Article ; Online: CT60 and +49 polymorphisms of CTLA 4 are associated with ANCA-positive small vessel vasculitis.

Kamesh, Lavanya / Heward, Joanne M / Williams, Julie M / Gough, Stephen C L / Chavele, Konstantia-Maria / Salama, Alan / Pusey, Charles / Savage, Caroline O S / Harper, Lorraine

Rheumatology (Oxford, England)

2009 Volume 48, Issue 12, Page(s) 1502–1505

Abstract: Objective: To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV).: Methods: The CTLA-4 CT60 (exon 4), +49 (exon 1) and -318 ( ... ...

Abstract	Objective: To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV). Methods: The CTLA-4 CT60 (exon 4), +49 (exon 1) and -318 (promoter region) genotypes were determined by PCR and restriction fragment length polymorphism (RFLP) in 222 white Caucasians of UK origin with SVV and 670 ethnically matched controls. Results: The CTLA-4 exon 1 (+49) and 4 (CT60) polymorphisms are associated with SVV (+49: chi(2) = 10.965, P = 0.004; CT60: chi(2) = 12.017, P = 0.002). Both disease-susceptible and disease-protective haplotypes have been identified in this cohort, and their frequencies are similar in the subtypes of WG and microscopic polyangiitis. Conclusion: This study provides further evidence that CTLA-4, a susceptibility locus for a number of common autoimmune diseases, may also be involved in the development of ANCA-associated SVV.
MeSH term(s)	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/genetics ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology ; Antigens, CD/genetics ; CTLA-4 Antigen ; Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide
Chemical Substances	Antigens, CD ; CTLA-4 Antigen ; CTLA4 protein, human
Language	English
Publishing date	2009-12
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kep280
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Article: A single nucleotide polymorphism in the CD40 gene on chromosome 20q (GD-2) provides no evidence for susceptibility to Graves' disease in UK Caucasians.

Heward, Joanne M / Simmonds, Matthew J / Carr-Smith, Jackie / Foxall, Helen / Franklyn, Jayne A / Gough, Stephen C L

Clinical endocrinology

2004 Volume 61, Issue 2, Page(s) 269–272

Abstract: Objective: A genome-wide screen in Graves' disease (GD) has shown linkage to chromosome 20q, designated GD-2. The gene encoding CD40, which stimulates lymphocyte proliferation and differentiation, maps to this region, and a single nucleotide ... ...

Abstract	Objective: A genome-wide screen in Graves' disease (GD) has shown linkage to chromosome 20q, designated GD-2. The gene encoding CD40, which stimulates lymphocyte proliferation and differentiation, maps to this region, and a single nucleotide polymorphism (SNP) at position -1 of the Kozak sequence within the gene has been reported to be associated with GD. The aim of this study was to determine whether this SNP of the CD40 gene confers susceptibility to GD in UK Caucasians. Design: A large case-control cohort consisting of 800 patients with GD, and 785 control subjects with no history of autoimmune disease, was used to genotype this SNP by polymerase chain reaction restriction fragment length polymorphism. Results: Despite adequate power (> 99%) to detect an effect, if present (odds ratio of 1.5), no significant difference in allele or genotype frequency of the CD40 SNP was observed between patients with GD and control subjects (P = 0.087 and P = 0.145, respectively). Conclusions: These data suggest that this polymorphism of the CD40 gene is not associated with GD in the UK and is therefore not contributing to disease susceptibility in the chromosomal region designated GD-2.
MeSH term(s)	Alleles ; CD40 Antigens/genetics ; Case-Control Studies ; Chromosomes, Human, Pair 20/genetics ; Cohort Studies ; European Continental Ancestry Group ; Gene Frequency ; Genetic Predisposition to Disease ; Graves Disease/genetics ; Humans ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide/genetics ; United Kingdom
Chemical Substances	CD40 Antigens
Language	English
Publishing date	2004-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121745-8
ISSN	1365-2265 ; 0300-0664
ISSN (online)	1365-2265
ISSN	0300-0664
DOI	10.1111/j.1365-2265.2004.02099.x
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Article: A nonsense mutation in exon 2 of the DNase I gene is not present in UK subjects with systemic lupus erythematosus and Graves' disease: Comment on the article by Rood et al.

Simmonds, Matthew J / Heward, Joanne M / Kelly, M Ann / Allahabadia, Amit / Foxall, Helen / Gordon, Caroline / Franklyn, Jayne A / Gough, Stephen C L

Arthritis and rheumatism

2002 Volume 46, Issue 11, Page(s) 3109–3110

MeSH term(s)	Codon, Nonsense ; Deoxyribonuclease I/genetics ; Exons/genetics ; Female ; Genetic Predisposition to Disease/genetics ; Graves Disease/genetics ; Humans ; Lupus Erythematosus, Systemic/genetics ; United Kingdom
Chemical Substances	Codon, Nonsense ; Deoxyribonuclease I (EC 3.1.21.1)
Language	English
Publishing date	2002-11
Publishing country	United States
Document type	Letter
ZDB-ID	127294-9
ISSN	1529-0131 ; 0004-3591 ; 2326-5191
ISSN (online)	1529-0131
ISSN	0004-3591 ; 2326-5191
DOI	10.1002/art.10414
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Article ; Online: Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease.

Boelaert, Kristien / Newby, Paul R / Simmonds, Matthew J / Holder, Roger L / Carr-Smith, Jacqueline D / Heward, Joanne M / Manji, Nilusha / Allahabadia, Amit / Armitage, Mary / Chatterjee, Krishna V / Lazarus, John H / Pearce, Simon H / Vaidya, Bijay / Gough, Stephen C / Franklyn, Jayne A

The American journal of medicine

2010 Volume 123, Issue 2, Page(s) 183.e1–9

Abstract: Background: Common autoimmune disorders tend to coexist in the same subjects and to cluster in families.: Methods: We performed a cross-sectional multicenter study of 3286 Caucasian subjects (2791 with Graves' disease; 495 with Hashimoto's ... ...

Abstract	Background: Common autoimmune disorders tend to coexist in the same subjects and to cluster in families. Methods: We performed a cross-sectional multicenter study of 3286 Caucasian subjects (2791 with Graves' disease; 495 with Hashimoto's thyroiditis) attending UK hospital thyroid clinics to quantify the prevalence of coexisting autoimmune disorders. All subjects completed a structured questionnaire seeking a personal and parental history of common autoimmune disorders, as well as a history of hyperthyroidism or hypothyroidism among parents. Results: The frequency of another autoimmune disorder was 9.67% in Graves' disease and 14.3% in Hashimoto's thyroiditis index cases (P=.005). Rheumatoid arthritis was the most common coexisting autoimmune disorder (found in 3.15% of Graves' disease and 4.24% of Hashimoto's thyroiditis cases). Relative risks of almost all other autoimmune diseases in Graves' disease or Hashimoto's thyroiditis were significantly increased (>10 for pernicious anemia, systemic lupus erythematosus, Addison's disease, celiac disease, and vitiligo). There was relative "clustering" of Graves' disease in the index case with parental hyperthyroidism and of Hashimoto's thyroiditis in the index case with parental hypothyroidism. Relative risks for most other coexisting autoimmune disorders were markedly increased among parents of index cases. Conclusion: This is one of the largest studies to date to quantify the risk of diagnosis of coexisting autoimmune diseases in more than 3000 index cases with well-characterized Graves' disease or Hashimoto's thyroiditis. These risks highlight the importance of screening for other autoimmune diagnoses if subjects with autoimmune thyroid disease present with new or nonspecific symptoms.
MeSH term(s)	Adult ; Age Distribution ; Aged ; Cluster Analysis ; Cohort Studies ; Cross-Sectional Studies ; Female ; Genetic Predisposition to Disease ; Graves Disease/complications ; Graves Disease/epidemiology ; Graves Disease/genetics ; Hashimoto Disease/complications ; Hashimoto Disease/epidemiology ; Hashimoto Disease/genetics ; Humans ; Male ; Middle Aged ; Prevalence ; Risk ; Sex Distribution ; United Kingdom/epidemiology
Language	English
Publishing date	2010-01-25
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	80015-6
ISSN	1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
ISSN (online)	1555-7162 ; 1873-2178
ISSN	0002-9343 ; 1548-2766
DOI	10.1016/j.amjmed.2009.06.030
Database	MEDical Literature Analysis and Retrieval System OnLINE

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