Gene-gene-sex interaction in cytokine gene polymorphisms revealed by serum interferon alpha phenotype in Juvenile dermatomyositis

Timothy B. Niewold, Silvia N. Kariuki, Gabrielle A. Morgan, Sheela Shrestha, Lauren M. Pachman

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Objective: To detect genetic polymorphisms associated with high serum interferon alpha (IFN-α) 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-α 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-α)-308 A alleles had significantly increased serum IFN-α 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-α -308A as compared with male carriers of TNF-α -308A (odds ratio >9.0; P = 7.2 x 10-3). Conclusion: These data support a complex gene-gene-sex interaction between the OPN and TNF-α promoter regions in JDM, defining a high serum IFN-α subgroup within JDM. This suggests pathogenic synergy between the OPN and TNF-α loci in female subjects with JDM, which may underlie some of the increased incidence of this condition in girls.

Original languageEnglish (US)
Pages (from-to)653-657
Number of pages5
Journaljournal of pediatrics
Issue number4
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


Dive into the research topics of 'Gene-gene-sex interaction in cytokine gene polymorphisms revealed by serum interferon alpha phenotype in Juvenile dermatomyositis'. Together they form a unique fingerprint.

Cite this