Cytotoxic T-Lymphocyte Associated Antigen 4 Gene Polymorphisms and Autoimmune Thyroid Disease: A Meta-Analysis

Kavvoura, Fotini K.; Akamizu, Takashi; Awata, Takuya; Ban, Yoshiyuki; Chistiakov, Dimitry A.; Frydecka, Irena; Ghaderi, Abbas; Gough, Stephen; Hiromatsu, Yuji; Płoski, Rafał; Wang, Pei‐Wen; Ban, Yoshio; Bednarczuk, Tomasz; Chistiakova, Emma I.; Chojm, Marcin; Heward, J. M.; Hiratani, Hitomi; Juo, Suh‐Hang Hank; Karabon, Lidia; Katayama, Shigehiro; Kurihara, Susumu; Liu, Rue‐Tsuan; Miyake, Ikuyo; Omrani, Gholamhossein Ranjbar; Pawlak, Edyta; Taniyama, Matsuo; Tozaki, Teruaki; Ioannidis, John P. A.

doi:10.1210/jc.2007-0147

Cited by 168 publications

(154 citation statements)

References 59 publications

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“…In the available literature, studies on the polymorphism of CTLA4 exon1 A49G have shown conflicting results. Indeed, some studies disagree with our findings and suggest significant associations with GD and HT for both 49A/G and CT60G/A (Chistiakov and Turakulov 2003;Kavvoura et al 2007;Furugaki et al 2004) while others suggest that CTLA4 leads to the production of thyroid autoantibodies but it does not contribute to AITD (Tomer et al 2001).…”

Section: Discussioncontrasting

confidence: 81%

“…AITD are complex diseases in which susceptibility genes, mainly HLA genes, have been identified to initiate the autoimmune response against the thyroid gland in complex with environmental triggers (Kavvoura et al 2007). There are at least two hypotheses concerning the existence of an association between an allele and a disease: (1) the allele itself is the genetic variant causing an increased risk for the disease and (2) the allele itself is not causing the disease but rather a gene in linkage disequilibrium with it.…”

Section: Discussionmentioning

confidence: 99%

“…Disease association studies show that the nature and location of HLA polymorphisms are of major importance (Erlich et al 1993). The CTLA-4 gene has been one of the most studied genes in relation to autoimmunity (Kavvoura et al 2007). It is an important co-stimulatory molecule that participates in the interaction between T cells and antigen-presenting cells.…”

Section: Introductionmentioning

confidence: 99%

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Genetics of autoimmune thyroid disease in the Lebanese population

et al. 2012

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This study aims to investigate the association of human leukocyte antigen (HLA) class II genes and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) with autoimmune thyroid diseases in the Lebanese population. A total of 128 patients with autoimmune thyroid disease (55 with Graves' disease (GD) and 73 with Hashimoto's thyroiditis (HT)) were typed for HLA DQA1 (0301 and 0501) and DQB1 (0201, 0302, and 0303) and for 49A/G CTLA-4 using PCR-based sequence-specific priming methods. A total of 186 matched controls were typed for the same alleles and compared to the diseased population. Results showed no significant differences in HLA DQB1*0201 or DQB1*0301 allelic frequencies or CTLA-4 polymorphisms between patients and controls. For GD, there was a weak association with HLA DQB1*0302 [34.6% (19 of 55)

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Section: Discussioncontrasting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetics of autoimmune thyroid disease in the Lebanese population

et al. 2012

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“…Analysis of CTLA-4 and HLA-DRB1 polymorphisms were reported previously. 32,33 Statistical analysis Allele frequencies were compared between groups by w 2 test on a 2 Â 2 contingency table using Statistica software package (StatSoft Inc., Tulsa, OK, USA). The genotype distribution was analyzed assuming three models of inheritance: dominant, codominant or recessive.…”

Section: Genotypingmentioning

confidence: 99%

Association of NFKB1 −94ins/del ATTG promoter polymorphism with susceptibility to and phenotype of Graves' disease

et al. 2007

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Recently, a functional polymorphism in the NFKB1 gene promoter (À94ins/del ATTG) has been identified and associated with chronic inflammatory diseases. The aim of this study was to analyze the association of NFKB1 polymorphism with susceptibility to and phenotype of Graves' disease (GD). The initial case-control association study, performed in a Polish-Warsaw cohort (388 GD patients and 688 controls), was followed by the two replication studies performed in Polish-Gliwice and JapaneseKurume cohorts (198 GD patients and 194 controls, and 424 GD patients and 222 controls, respectively). The frequency of the À94del ATTG (D) allele was increased in GD compared to controls in Warsaw cohort. This finding was replicated in Gliwice cohort. Combining both Polish-Caucasian cohorts showed that the NFKB1 polymorphism was significantly associated with susceptibility to GD with a codominant mode of inheritance (P ¼ 0.00005; OR ¼ 1.37 (1.18-1.60)). No association with GD was found in Japanese cohort. However, subgroup analysis in Japanese GD patients revealed a correlation between the NFKB1genotype and the development of ophthalmopathy (P ¼ 0.009; OR ¼ 1.49 (1.10-2.01)), and the age of disease onset (P ¼ 0.009; OR ¼ 1.45 (1.09-1.91)). Our results suggest that NFKB1 À94ins/del ATTG polymorphism may be associated with susceptibility to and/or phenotype of GD.

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“…10 CTLA4 encodes a co-stimulatory molecule of T cells, which is involved in the regulation of T-cell activation, 11,12 and it has been reported that the polymorphisms in exon 1 and 3¢-UTR region are associated with GD as well as Hashimoto thyroiditis, another autoimmune thyroid disease, in European and Asian populations. 10,[13][14][15] However, it is not clear how the CTLA4 and HLA polymorphisms would confer the risk to GD; that is, they operate independently or synergistically in determining the genetic risk. To clarify the issue, we analyzed a CTLA4 polymorphism (rs3087243, also called as CT60) in addition to HLA-A*02, DPB1*0202 and DPB1*0501 in association with GD.…”

Section: Introductionmentioning

confidence: 99%

HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves’ disease

Takahashi

Kimura

2010

J Hum Genet

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Graves' disease (GD) is an autoimmune disease characterized by hyperthyroidism due to the presence of autoantibodies against thyroid-stimulating hormone receptor, which is measured as thyroid-stimulating hormone-binding inhibitory immunoglobulin (TBII). Most of the GD patients are TBII-positive, but TBII is undetectable in a proportion of GD patients. We previously reported the association of HLA-A*02 and -DPB1*0501 with TBII-positive GD, whereas TBII-negative GD showed association with HLA-A*02 and DPB1*0202. Recently, polymorphisms of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) gene are reported to be associated with GD. In this study, we investigated 329 (240 TBII-positive and 89 TBII-negative) GD patients and 378 controls for the polymorphisms in HLA-A, -DPB1 and CTLA4 (CT60, rs3087243, A/G) to investigate the contribution of these factors in the susceptibility to GD. A significant association with CTLA4 was found for the TBII-positive GD (G carriers in patients vs controls, 97.1 vs 91.8%; odds ratio (OR)¼2.97, 95% confidence interval¼1.29-6.87, P¼0.008), but the association was weak and not significant for the TBII-negative GD (94.4 vs 91.8%; OR¼1.50, 95% confidence interval¼0.57-3.98, P¼0.41). Stratification analyses suggested a possible synergistic interaction of CTLA4 with HLA-A*02 and -DPB1*0501 in the susceptibility to TBII-positive GD. INTRODUCTIONGraves' disease (GD) is a typical organ-specific autoimmune disease affecting thyroid gland, in which autoantibodies against the receptors for thyroid-stimulating hormone induce hyperthyroidism. The autoantibodies has been measured as thyroid-stimulating antibodies (TSAb) by a biological assay or as thyroid-stimulating hormonebinding inhibitory immunoglobulins (TBII) by a solid phase assay. 1 Although most of the GD patients are positive for both TBII and TSAb, a proportion of the patients carry low or undetectable level of TBII (TBII-negative GD). 2 However, TSAb can be detected in the TBII-negative GD, and it was reported that the TBII-negative patients exhibited mild goiter and followed benign prognosis, implying that the TBII-negative GD might be a clinical subtype different from the ordinary TBII-positive GD. 3 Etiological mechanisms of GD are not fully understood, but certain genetic factors should be involved in the pathogenesis because of familial aggregation of the disease. 4 To decipher the genetic factors candidate gene approaches have been used, and it is well documented that human leukocyte antigen (HLA) polymorphisms are associated with GD, such that HLA-B*08-DRB1*03-DQA1*05-DQB1*02 haplotype showed strong association in European populations. 5,6 However, the distribution of HLA alleles and haplotypes are quite different in different ethnic groups, and the European GD-associated HLA haplotype is virtually absent in Japanese. 7 We previously reported that HLA-A*02 and DPB1*0501 are associated with Japanese GD. 8 In addition, we demonstrated that HLA-A*02 and DPB1*0202 showed association with TBII-negative GD, indicating that the T...

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Cytotoxic T-Lymphocyte Associated Antigen 4 Gene Polymorphisms and Autoimmune Thyroid Disease: A Meta-Analysis

Abstract: The CT60 polymorphism of CTLA-4 maps an important genetic determinant for the risk of both GD and HT across diverse populations.

Cited by 168 publications

References 59 publications

Genetics of autoimmune thyroid disease in the Lebanese population

Genetics of autoimmune thyroid disease in the Lebanese population

Association of NFKB1 −94ins/del ATTG promoter polymorphism with susceptibility to and phenotype of Graves' disease

HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves’ disease

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