TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility

Peluso, Carla; Christofolini, Denise Maria; Goldman, Cecilia; Mafra, Fernanda; Cavalcanti, Viviane; Barbosa, Caio Parente; Bianco, Bianca

doi:10.1016/j.humimm.2012.09.007

Cited by 23 publications

(16 citation statements)

References 42 publications

(47 reference statements)

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“…In our study, the minor allele frequency (MAF) for rs2304256 (A-allele) observed in the childhood control was 23.4 (95% CI, 17-30), and in the adult control it was 24.7% (95% CI, 20-35). This was similar to those observed in healthy Brazilian (23.6%) (Peluso et al, 2013) and European (27.9%) (Lopez-Isac et al, 2016) populations. The frequency of the A-allele in a healthy Asian population (Chinese [42.4%] and in Japanese [38.3%] (Kyogoku et al, 2009) was significantly higher than that obtained in our study.…”

Section: Discussionsupporting

confidence: 91%

Brief Note Polymorphism V362F (rs2304256) of tyrosine kinase 2 is not associated with childhood- or adulthood-onset type 1 diabetes in southern Brazil

Graciolo¹,

Welter²,

Campos³

et al. 2019

Genet. Mol. Res.

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Type 1 diabetes mellitus (T1D) is considered a polygenic disease that is influenced by environmental factors and autoimmune responses to autoantibodies, resulting in metabolic abnormalities. Tyrosine kinase 2 (TYK2) is involved in type I interferon signaling in beta cells, and TYK2 polymorphism rs2304256 has been associated with T1D. We investigated polymorphism rs2304256 (TYK2) in a case-control study of Euro-Brazilians with T1D manifested during childhood and adulthood. We studied 307 individuals manifesting clinical signs of type 1 diabetes (151 children below 14 years of age and 156 adults with diagnosis after 18 years of age). The control samples consisted of 169 healthy children and 150 healthy adult subjects. T1D groups had inadequate glycemic control because fasting glucose and mean HbA1C concentrations were significantly higher than in the control groups. Real-time PCR with

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Section: Discussionsupporting

confidence: 91%

Brief Note Polymorphism V362F (rs2304256) of tyrosine kinase 2 is not associated with childhood- or adulthood-onset type 1 diabetes in southern Brazil

Graciolo¹,

Welter²,

Campos³

et al. 2019

Genet. Mol. Res.

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“…Many SNPs are in the coding region, and .100 nonsynonymous variants have been annotated. Genome-wide association studies and more targeted candidate approaches have shown strong linkage of Tyk2 haplotypes or individual SNPs to systemic and organ-specific autoimmune diseases, namely systemic lupus erythematosus (SLE) (11)(12)(13)(14), multiple sclerosis (MS) (15)(16)(17)(18)(19), Crohn's disease (20)(21)(22), psoriasis (23), type 1 diabetes (24), endometriosis-related infertility (25), and primary biliary cirrhosis (26) (Table I). Interestingly, one rare MSassociated variant (rs34536443) is considered to be protective, whereas another (rs55762744) was recently identified as a risk allele (17).…”

mentioning

confidence: 99%

Two Rare Disease-Associated Tyk2 Variants Are Catalytically Impaired but Signaling Competent

Gakovic

Ragimbeau

et al. 2013

The Journal of Immunology

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Tyk2 belongs to the Janus protein tyrosine kinase family and is involved in signaling of immunoregulatory cytokines (type I and III IFNs, IL-6, IL-10, and IL-12 families) via its interaction with shared receptor subunits. Depending on the receptor complex, Tyk2 is coactivated with either Jak1 or Jak2, but a detailed molecular characterization of the interplay between the two enzymes is missing. In human populations, the Tyk2 gene presents high levels of genetic diversity with >100 nonsynonymous variants being detected. In this study, we characterized two rare Tyk2 variants, I684S and P1104A, which have been associated with susceptibility to autoimmune disease. Specifically, we measured their in vitro catalytic activity and their ability to mediate Stat activation in fibroblasts and genotyped B cell lines. Both variants were found to be catalytically impaired but rescued signaling in response to IFN-α/β, IL-6, and IL-10. These data, coupled with functional study of an engineered Jak1 P1084A, support a model of nonhierarchical activation of Janus kinases in which one catalytically competent Jak is sufficient for signaling provided that its partner behaves as proper scaffold, even if inactive. Through the analysis of IFN-α and IFN-γ signaling in cells with different Jak1 P1084A levels, we also illustrate a context in which a hypomorphic Jak can hamper signaling in a cytokine-specific manner. Given the multitude of Tyk2-activating cytokines, the cell context–dependent requirement for Tyk2 and the catalytic defect of the two disease-associated variants studied in this paper, we predict that these alleles are functionally significant in complex immune disorders.

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“…It was previously reported in the Brazilian population that polymorphisms in the nuclear factor-κB gene promoter, B lymphocyte stimulator gene promoter and TYK2 were associated with endometriosis-related infertility. 33, 34, 35 Nevertheless, we report here for the first time that in the Chinese Han population the CYP19 rs700518 AA genotype is associated with endometriosis-related infertility. This result indicates clinical relevance with regard to two aspects.…”

Section: Discussionmentioning

confidence: 59%

CYP19 gene variant confers susceptibility to endometriosis-associated infertility in Chinese women

Wang

et al. 2014

Exp Mol Med

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An aromatase encoded by the CYP19 gene catalyzes the final step in the biosynthesis of estrogens, which is related to endometriosis development. To assess the association of CYP19 gene polymorphisms with the risks of endometriosis, chocolate cysts and endometriosis-related infertility, a case–control study was conducted in Chinese Han women by recruiting 225 healthy control females, 146 patients with endometriosis, 94 endometriosis women with chocolate cyst and 65 women with infertility resulting from endometriosis, as diagnosed by both pathological and laparoscopic findings. Individual genotypes at rs2236722:T>C, rs700518:A>G, rs10046:T>C and [TTTA]n polymorphisms were identified. Allelic and genotypic frequencies were compared between the control group and case groups by chi-square analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined by logistic regression analysis to predict the association of CYP19 gene polymorphisms with the risk of endometriosis, the related chocolate cysts and infertility. The genotype distributions of the tested CYP19 gene polymorphisms were not significantly different between the healthy control group and the endometriosis/endometriosis with the chocolate cyst group. However, the CYP19 rs700518AA genotype was significantly associated with an increased risk of endometriosis-related infertility (55.4% in the infertility group vs 25.3% in the control group, P<0.001; OR (95% CI): 3.66 (2.06–6.50)) under the recessive form of the A allele. Therefore, we concluded that in Chinese Han females CYP19 gene polymorphisms are not associated with susceptibility to endometriosis or chocolate cysts, whereas CYP19 rs700518AA genotype confers genetic susceptibility to endometriosis-related infertility.

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TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility

Cited by 23 publications

References 42 publications

Brief Note Polymorphism V362F (rs2304256) of tyrosine kinase 2 is not associated with childhood- or adulthood-onset type 1 diabetes in southern Brazil

Brief Note Polymorphism V362F (rs2304256) of tyrosine kinase 2 is not associated with childhood- or adulthood-onset type 1 diabetes in southern Brazil

Two Rare Disease-Associated Tyk2 Variants Are Catalytically Impaired but Signaling Competent

CYP19 gene variant confers susceptibility to endometriosis-associated infertility in Chinese women

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