Non-HLA autoimmunity genetic factors contributing to Autoimmune Polyglandular Syndrome type II in Tunisian patients

Fourati, H.; Bouzid, Dorra; Abida, Olfa; Kharrat, Najla; Mnif, F.; Haddouk, Samy; Fesel, Constantin; Costa, João; Ayed, M. Ben; Abid, M.; Rebai, Ahmed; Penha‐Gonçalves, Carlos; Masmoudi, Hatem

doi:10.1016/j.humimm.2012.04.013

Cited by 12 publications

(9 citation statements)

References 49 publications

(62 reference statements)

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“…Former studies have corroborated the association of stat4 polymorphism with two other major components of the autoimmune polyendocrine syndrome type 2, such as Addison's disease and autoimmune thyroid disease [24][25][26]29]. Observations in small cohorts with polyglandular autoimmunity equally confirm its implication in multiple organ-specific disorders [32,40]. Taken together, similar to previously identified immune regulatory loci such as PtPn22 and CtLa4, stat4 seems to be universally engaged in maintenance of the immune homeostasis [41].…”

Section: Discussionsupporting

confidence: 63%

STAT4 sequence variant and elevated gene expression are associated with type 1 diabetes in Polish children

Fichna

Żurawek

Bogusz‐Górna

et al. 2020

cejoi

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Introduction: type 1 diabetes (t1D) is caused by the autoimmune destruction of pancreatic β cells, resulting from coincident genetic predisposition and some environmental triggers. signal transducer and activator of transcription 4 (stat4) gene encodes a transcription factor, which promotes th1 cell differentiation, interferon γ production, and development of th17 cells. Polymorphisms of stat4 are associated with several autoimmune conditions, while studies in t1d provided inconsistent results. this analysis was designed to investigate the association of stat4 rs7574865 with t1d in Polish children and to assess stat4 expression in newly diagnosed subjects. Material and methods: rs7574865 was genotyped in 656 t1d children and 782 healthy individuals. stat4 mrna expression was analyzed in peripheral blood mononuclear cells (PBMcs) from 29 children with t1d and 27 age-matched controls. β-cell and thyroid-specific serum autoantibodies were assessed with radioimmunoassays. Results: the distribution of rs7574865 genotypes and alleles demonstrated significant difference (p = 0.002, p < 0.001, respectively) between patients vs. controls. carriers of the minor t allele presented earlier t1d onset (p = 0.017). no differences were found in β-cell autoantibody in genotype-stratified patients (p > 0.050), while anti-thyroid antibodies were more frequent in carriers of the minor allele (p = 0.039 for anti-thyroperoxidase, p = 0.007 for anti-thyroglobulin antibodies, respectively). stat4 was overexpressed in PBMcs from t1d patients (p = 0.008), especially subjects with two/three circulating β-cell antibodies (p < 0.001). Conclusions: the study confirms an association of stat4 rs7574865 with t1d in Polish patients, and provides an evidence for its relationship with an earlier disease onset and concomitant thyroid autoimmunity. stat4 expression appears elevated in t1d, especially with more severe reaction against β-cell antigens.

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Section: Discussionsupporting

confidence: 63%

STAT4 sequence variant and elevated gene expression are associated with type 1 diabetes in Polish children

Fichna

Żurawek

Bogusz‐Górna

et al. 2020

cejoi

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“…This finding suggests that this cytokine might be involved in the common pathways underlying the development of multiple autoimmune diseases. Fourati et al (2012) found an association of the rs1800629 SNP with APSIII in Tunisian patients, although they compared APSIII individuals with healthy controls. Therefore, as the published results for TNF-α are weak and controversial, more replica studies are needed.…”

Section: Discussionmentioning

confidence: 99%

Association of TNF-α, CTLA4, and PTPN22 polymorphisms with type 1 diabetes and other autoimmune diseases in Brazil

Tavares¹,

Santos²,

Moura³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Type 1 diabetes mellitus (T1D) is a complex disorder characterized by an autoimmune response against human pancreatic beta-cells. Patients with T1D can also develop a response toward one or more other factors, such as in autoimmune thyroiditis (AITD) and celiac disease (CD). In the presence of T1D + AITD, the patient is diagnosed with autoimmune polyglandular syndrome type III (APSIII); patients with APSIII may also present with CD. These diseases have a strong genetic component and share many susceptibility genes, suggesting potentially overlapping pathogenic pathways. Polymorphisms in the TNF-α (rs1800629), CTLA-4 (rs231775), and PTPN22 (rs2476601) genes have been previous associated with T1D; however, there is no consensus regarding their role in T1D and scarce literature focusing on AIDT and/or CD. Thus, we analyzed these genetic variants in 205 Northeast Brazilian patients with T1D and with/without AITD and/or CD, and in 308 healthy controls. The PTPN22 gene variants were associated with T1D susceptibility and APSIII [odds ratio (OR) = 2.57 and 2.77, respectively]. CTLA4 rs231775 and TNF-α rs1800629 were not associated with T1D onset in the Brazilian population. However, when comparing APSIII individuals in the T1D only group, we observed an association of the TNF-α SNP in the allelic (P = 0.0442; OR = 0.44) and dominant models (P = 0.0387; OR = 0.40). This study reinforces the importance of CTLA-4 and other variants in unraveling the pathogenic mechanisms of T1D in different populations and in understanding their relationships with the development of other T1D-related autoimmune diseases.

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“…Moreover, this polymorphism was strongly associated with T1D in a northeastern Chinese population (Bi et al, 2013). Additionally, the study performed by Fourati et al (2012) assessed the possible role of non-HLA genes in APSII, which includes Addison's disease and AITD and/or T1D, in a Tunisian population. Their results indicated that the rs7574865 SNP in STAT4 was associated with APSII but not with T1D or AITD alone, suggesting that STAT4 is involved with the co-occurrence of autoimmune endocrinopathies in APSII individuals.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of STAT4 and IFIH1 polymorphisms in type 1 diabetes mellitus patients with autoimmune polyglandular syndrome type III

Silva¹,

Tavares²,

Santos³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Type 1 diabetes mellitus (T1D) is an organ-specific autoimmune disease characterized by T-cell mediated self-destruction of insulinproducing β cells in the pancreas. T1D patients are prone to develop other glandular autoimmune disorders, such as autoimmune thyroid disease that occurs simultaneously with autoimmune polyglandular syndrome type III (APSIII). Signal transducer and activator of transcription 4 (STAT4) is a wellknown regulator of proinflammatory cytokines, and interferon-induced with helicase C domain 1 (IFIH1) is activated in the interferon type I response. Both genes have been examined separately in autoimmune diseases and, 17731STAT4 and IFIH1 SNPs in T1D and APSIII ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 17730-17738 (2015) in this study, we assessed their joint role in T1D and APSIII. We conducted a case-control study, enrolling 173 T1D patients and 191 healthy controls from northeastern Brazil, to assess the distribution of the rs7574865 and rs3024839 SNPs in STAT4 and the rs3747517 and rs1990760 SNPs in IFIH1 in T1D and APSIII patients. Additionally, we conducted a metaanalysis with the rs7574865 SNP in STAT4 (1392 T1D patients and 1629 controls) and the rs1990760 SNP in IFIH1 (25092 T1D patients and 28544 controls) to examine their association with T1D. Distribution of STAT4 and IFIH1 allelic frequencies did not show statistically significant differences between T1D patients and controls in our study population; however, the meta-analysis indicated that SNPs in STAT4 and IFIH1 are associated with T1D worldwide. Our findings indicate that although STAT4 and IFIH1 SNPs are not associated with T1D in a Brazilian population, they might play a role in susceptibility to T1D on a larger worldwide scale.

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Non-HLA autoimmunity genetic factors contributing to Autoimmune Polyglandular Syndrome type II in Tunisian patients

Cited by 12 publications

References 49 publications

STAT4 sequence variant and elevated gene expression are associated with type 1 diabetes in Polish children

STAT4 sequence variant and elevated gene expression are associated with type 1 diabetes in Polish children

Association of TNF-α, CTLA4, and PTPN22 polymorphisms with type 1 diabetes and other autoimmune diseases in Brazil

Meta-analysis of STAT4 and IFIH1 polymorphisms in type 1 diabetes mellitus patients with autoimmune polyglandular syndrome type III

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