Gene-gene-sex Interaction in Cytokine Gene Polymorphisms Revealed by Serum Interferon Alpha Phenotype in Juvenile Dermatomyositis

Overview

Journal J Pediatr

Specialty Pediatrics

Date 2010 Jul 8

PMID 20605164

Citations 23

Authors

Timothy B Niewold

Silvia N Kariuki

Gabrielle A Morgan

Sheela Shrestha

Lauren M Pachman

Affiliations

Soon will be listed here.

Abstract

Objective: To detect genetic polymorphisms associated with high serum interferon alpha (IFN-alpha) levels in juvenile dermatomyositis (JDM) and explore interactions in associated polymorphisms.

Study Design: Eighty-five children of European ancestry with definite/probable JDM were studied. Selected genetic polymorphisms that were associated with high IFN-alpha levels in 12 untreated patients with newly diagnosed JDM were genotyped in a validation cohort of 73 children with JDM and analyzed for gene-gene and gene-sex interactions.

Results: Untreated children with newly diagnosed JDM carrying both the osteopontin (OPN) rs28357094G and tumor necrosis factor alpha (TNF-alpha)-308 A alleles had significantly increased serum IFN-alpha levels. These 2 polymorphisms were genotyped in the validation cohort, and the OPN rs28357094G allele was more common in female subjects with JDM (odds ratio=3.97, P=.012). This OPN allele was most strongly enriched in female carriers of TNF-alpha-308A as compared with male carriers of TNF-alpha-308A (odds ratio>9.0; P=7.2x10(-3)).

Conclusion: These data support a complex gene-gene-sex interaction between the OPN and TNF-alpha promoter regions in JDM, defining a high serum IFN-alpha subgroup within JDM. This suggests pathogenic synergy between the OPN and TNF-alpha loci in female subjects with JDM, which may underlie some of the increased incidence of this condition in girls.

Citing Articles

Juvenile dermatomyositis and nephrotic syndrome: A case report and a mini literature review.

Zhou W, Dong L, Liu X, Dong C, Zhang H Front Pediatr. 2023; 11:1149785.

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Advancements in the Treatment of Cutaneous Lupus Erythematosus and Dermatomyositis: A Review of the Literature.

Elhage K, Zhao R, Nakamura M Clin Cosmet Investig Dermatol. 2022; 15:1815-1831.

PMID: 36105749 PMC: 9467686. DOI: 10.2147/CCID.S382628.

Type I Interferons in Autoimmunity.

Fernandez-Ruiz R, Niewold T J Invest Dermatol. 2022; 142(3 Pt B):793-803.

PMID: 35016780 PMC: 8860872. DOI: 10.1016/j.jid.2021.11.031.

Systemic and Tissue Inflammation in Juvenile Dermatomyositis: From Pathogenesis to the Quest for Monitoring Tools.

Wienke J, Deakin C, Wedderburn L, van Wijk F, Royen-Kerkhof A Front Immunol. 2019; 9:2951.

PMID: 30619311 PMC: 6305419. DOI: 10.3389/fimmu.2018.02951.

Advances in Juvenile Dermatomyositis: Myositis Specific Antibodies Aid in Understanding Disease Heterogeneity.

Pachman L, Khojah A J Pediatr. 2018; 195:16-27.

PMID: 29576174 PMC: 5881602. DOI: 10.1016/j.jpeds.2017.12.053.

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