Interaction of HLA-DRB1 Alleles with CTLA-4 in the Predisposition to Graves' Disease: The Impact of DRB1*07

Kula, Dorota; Bednarczuk, Tomasz; Jurecka‐Lubieniecka, Beata; Polańska, Joanna; Hasse-Lazar, Kornelia; Jarząb, Michał; Steinhof-Radwańska, Katarzyna; Hejduk, B.; Zebracka, Jadwiga; Kuryłowicz, Alina; Bar-Andziak, Ewa; Stechly, Tomasz; Pawlaczek, Agnieszka; Gubała, E; Krawczyk, Agnieszka; Szpak‐Ulczok, Sylwia; Nauman, J; Jarząb, Barbara

doi:10.1089/thy.2006.16.447

Cited by 25 publications

(22 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study we have shown that the frequency of the polymorphic GG genotype at position 49 of exon 1 of the CTLA-4 gene is significantly increased in Polish HT children compared to the control group. These results confirm the association between A/G49 CTLA-4 gene polymorphism and AITD reported previously in the Polish population by other authors [25,26]. In the present study the mean concentration of anti-Tg Abs was significantly higher in sera from GG homozygous patients compared to wild AA homozygotes.…”

Section: Discussionsupporting

confidence: 93%

Association between the Polymorphism A/G at Position 49 of Exon 1 of the CTLA-4 Gene and Antithyroid Antibody Production in Children with Hashimoto’s Thyroiditis

et al. 2012

View full text Add to dashboard Cite

CTLA-4 gene is considered to be one of the strongest factors determining the predisposition to antithyroid antibody (Ab) production. The aim of the study was to evaluate the association of the polymorphism A/G of exon 1 of CTLA-4 gene and antithyroid Ab level in children with Hashimoto’s thyroiditis (HT). Material and Methods: 45 children with HT (aged 14.9 ± 2, range 8.1–7.9) and 55 healthy controls (aged 14.8 ± 2.34, range 8.0–17.4) were enrolled. Controls were euthyroid and free from any autoimmune disease. CTLA-4 gene (+49)A/G polymorphism was evaluated by a single-strand conformation polymorphism method and restriction fragment-length polymorphism. Results: The frequency of GG genotype in HT children was significantly higher than in controls: 31 vs. 14.5% respectively (p < 0.04, OR = 2.65, CI = 0.99–7.06). Anti-Tg Ab titers were higher in patients homozygous for G allele than with AA genotype. The GG genotype seemed to be protective from hypothyroidism at the moment of HT diagnosis, but this observation was not statistically confirmed. Conclusions: Our study provides the evidence supporting the association between CTLA-4 gene (+49)A/G polymorphism and the susceptibility to HT in Polish children and confirms the existence of a link between (+49)A/G polymorphism and anti-Tg Ab level.

show abstract

Section: Discussionsupporting

confidence: 93%

Association between the Polymorphism A/G at Position 49 of Exon 1 of the CTLA-4 Gene and Antithyroid Antibody Production in Children with Hashimoto’s Thyroiditis

et al. 2012

View full text Add to dashboard Cite

show abstract

“…HLA-DRB1 typing was performed using sequence-specific oligonucleotides (SSO, Innolipa HLA-DRB1, Innogenetics, Gent, Belgium) and sequence-specific primers (MSSP Class II DRB Only, One Lambda, Dynal All Set SSP DR test, Dynal Biotech, Oslo, Norway) (Kula 2006) [25] in the Gliwice study, and by Dynal All Set SSP Dr test (Dynal Biotech, Bromborough, Wirral, UK) in the Warsaw study (Bednarczuk 2004) [26]. CTLA-4 and PTPN22 were analysed by PCF-RFLP methods, as previously described (Jurecka-Lubieniecka 2013 [27], Kula 2006 [25], Bednarczuk 2003 [28], Skórka 2005 [29]) [Table 1]. In the Gliwice study PCR was performed with 0.5 units Hot Star Taq polymerase (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

Association between Polymorphisms in the TSHR Gene and Graves' Orbitopathy

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundGraves' orbitopathy (GO) as well as Graves' disease (GD) hyperthyroidism originate from an autoimmune reaction against the common auto-antigen, thyroid-stimulating hormone receptor (TSHR). GO phenotype is associated with environmental risk factors, mainly nicotinism, as well as genetic risk factors which initiate an immunologic reaction. In some patients GO is observed before diagnosis of GD hyperthyroidism, while it can also be observed far after diagnosis. The intensity of GO symptoms varies greatly in these patients. Thus, the pathogenesis of GD and GO may correlate with different genetic backgrounds, which has been confirmed by studies of correlations between GO and polymorphisms in cytokines involved in orbit inflammation. The aim of our analysis was to assess genetic predisposition to GO in young patients (age of diagnosis ≤30 years of age), for whom environmental effects had less time to influence outcomes than in adults.Methods768 GD patients were included in the study. 359 of them had clinically evident orbitopathy (NOSPECS ≥2). Patients were stratified by age at diagnosis. Association analyses were performed for genes with a known influence on development of GD - TSHR, HLA-DRB1, cytotoxic T-lymphocyte antigen 4 (CTLA4) and lymphoid protein tyrosine phosphatase (PTPN22).ResultsThe rs179247 TSHR polymorphism was associated with GO in young patients only. In young GO-free patients, allele A was statistically more frequent and homozygous carriers had a considerable lower risk of disease incidence than patients with AG or GG genotypes. Those differences were not found in either elderly patients or the group analyzed as a whole.ConclusionsAllele A of the rs179247 polymorphism in the TSHR gene is associated with lower risk of GO in young GD patients.

show abstract

“…At present it is not clear which locus is responsible for the observed association. Out of the three most frequently studied genes encoded on this haplotype DQB1 *02 can be excluded as it is commonly found on haplotypes encoding DRB1 *07 which appear to protect from GD [23-25]. Conversely, the relative importance of DQA1 *05 and/or DRB1 *03 is under discussion.…”

Section: Genes Predisposing To Gdmentioning

confidence: 99%

The Genetic Basis of Graves Disease

Płoski

Szymański²,

Bednarczuk

2011

Self Cite

View full text Add to dashboard Cite

The presented comprehensive review of current knowledge about genetic factors predisposing to Graves’ disease (GD) put emphasis on functional significance of observed associations. In particular, we discuss recent efforts aimed at refining diseases associations found within the HLA complex and implicating HLA class I as well as HLA-DPB1 loci. We summarize data regarding non-HLA genes such as PTPN22, CTLA4, CD40, TSHR and TG which have been extensively studied in respect to their role in GD. We review recent findings implicating variants of FCRL3 (gene for FC receptor-like-3 protein), SCGB3A2 (gene for secretory uteroglobin-related protein 1- UGRP1) as well as other unverified possible candidate genes for GD selected through their documented association with type 1 diabetes mellitus: Tenr–IL2–IL21, CAPSL (encoding calcyphosine-like protein), IFIH1(gene for interferon-induced helicase C domain 1), AFF3, CD226 and PTPN2. We also review reports on association of skewed X chromosome inactivation and fetal microchimerism with GD. Finally we discuss issues of genotype-phenotype correlations in GD.

show abstract

Interaction of HLA-DRB1 Alleles with CTLA-4 in the Predisposition to Graves' Disease: The Impact of DRB1*07

Cited by 25 publications

References 40 publications

Association between the Polymorphism A/G at Position 49 of Exon 1 of the <b><i>CTLA-4</i></b> Gene and Antithyroid Antibody Production in Children with Hashimoto’s Thyroiditis

Association between the Polymorphism A/G at Position 49 of Exon 1 of the <b><i>CTLA-4</i></b> Gene and Antithyroid Antibody Production in Children with Hashimoto’s Thyroiditis

Association between Polymorphisms in the TSHR Gene and Graves' Orbitopathy

The Genetic Basis of Graves Disease

Contact Info

Product

Resources

About