Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis

Ellis, Justine A.; Scurrah, Katrina J; Li, Yun R.; Ponsonby, Anne–Louise; Chavez, Raul A; Pezic, Angela; Dwyer, Terence; Akikusa, Jonathan; Allen, Roger C.; Becker, Mara L.; Thompson, Susan D.; Lie, Benedicte A.; Flatø, Berit; Førre, Ø; Punaro, Marilynn; Wise, Carol A.; Finkel, Terri H.; Hákonarson, Hákon; Munro, Jane

doi:10.1016/j.jsbmb.2014.10.012

Cited by 22 publications

(21 citation statements)

References 38 publications

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“…We therefore performed a sensitivity analysis using a Europeanrestricted 11 subset of the CLARITY sample (n case = 250 and n control = 423). Overall, and sex-specific, associations remained evident (Supplementary Table 1), as did statistically significant evidence for an interaction between genotype and sex (P interaction = 0.02).…”

Section: Resultsmentioning

confidence: 99%

“…11,17 Cases were diagnosed by a pediatric rheumatologist and classified into subtypes according to their clinical course. Participants included 413 cases (67% female, mean age 9.1 years) and 690 controls (42% female, mean age 7.1 years).…”

Section: Discovery Samplementioning

confidence: 99%

“…11 Genotype data for rs2476601 were extracted from genome-wide SNP data for 1008 cases (69% female) and 9284 controls (46% female) of European ancestry. Logistic regression was performed in PLINK 20 to test for association between rs2476601, total JIA and JIA subtypes, including sex-adjusted and sex-stratified analyses.…”

Section: Discovery Samplementioning

confidence: 99%

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The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females

Chiaroni-Clarke

Munro

et al. 2015

Genes Immun

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A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.52-3.63, P=0.00011) but not males (OR=0.91, 95% CI=0.52-1.60, P=0.75). This was similarly observed in the replication sample. There was evidence for genotype-by-sex interaction (Pinteraction=0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.

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Section: Resultsmentioning

confidence: 99%

Section: Discovery Samplementioning

confidence: 99%

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The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females

Chiaroni-Clarke

Munro

et al. 2015

Genes Immun

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“…Vitamin D regulates the innate and adaptive immune systems by activating the vitamin D receptor, which is distributed widely on immune cells (7,8). Consequently, vitamin D deficiency is associated with autoimmune diseases such as diabetes, rheumatoid arthritis, systemic lupus erythematosus, and JIA (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). A previous study reported suboptimal vitamin D levels in JIA patients (13).…”

Section: Introductionmentioning

confidence: 99%

Adjunctive vitamin D for the treatment of active juvenile idiopathic arthritis: An open‑label, prospective, randomized controlled trial

et al. 2019

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“…PTPN2, an intracellular tyrosine‐specific phosphatase, was recently found to regulate immune and inflammatory responses in diabetic patients as a protein downstream of the vitamin D receptor (VDR) . In the presence of proinflammatory stimuli, such as TNF‐α and IFN‐γ, or hyperosmotic stress, the nuclear isoform (TC45) of PTPN2 might translocate to the cytoplasm to exert its biological functions .…”

Section: Introductionmentioning

confidence: 99%

25‐Hydroxyvitamin D₃‐enhanced PTPN2 positively regulates periodontal inflammation through the JAK/STAT pathway in human oral keratinocytes and a mouse model of type 2 diabetes mellitus

Zhang

et al. 2018

J of Periodontal Research

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PTPN2 contributed to a decrease in periodontal inflammation in type 2 diabetes mellitus via dephosphorylate protein substrates in the JAK1/STAT3 signaling pathway after 25VD treatment in human oral keratinocytes and a mouse model of type 2 diabetes mellitus. A thorough understanding of PTPN2 and its involvement in inhibiting inflammation might provide alternative therapeutic approaches for the pathogenesis and treatment of diabetes mellitus-associated periodontitis.

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Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis

Cited by 22 publications

References 38 publications

The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females

The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females

Adjunctive vitamin D for the treatment of active juvenile idiopathic arthritis: An open‑label, prospective, randomized controlled trial

25‐Hydroxyvitamin D₃‐enhanced PTPN2 positively regulates periodontal inflammation through the JAK/STAT pathway in human oral keratinocytes and a mouse model of type 2 diabetes mellitus

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Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis

Cited by 22 publications

References 38 publications

The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females

The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females

Adjunctive vitamin D for the treatment of active juvenile idiopathic arthritis: An open‑label, prospective, randomized controlled trial

25‐Hydroxyvitamin D3‐enhanced PTPN2 positively regulates periodontal inflammation through the JAK/STAT pathway in human oral keratinocytes and a mouse model of type 2 diabetes mellitus

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25‐Hydroxyvitamin D₃‐enhanced PTPN2 positively regulates periodontal inflammation through the JAK/STAT pathway in human oral keratinocytes and a mouse model of type 2 diabetes mellitus