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

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• 作者：Timothy B. Niewold ; Silvia N. Kariuki ; Gabrielle A. Morgan ; Sheela Shrestha ; Lauren M. Pachman
• 刊名：The Journal of Pediatrics
• 出版年：2010
• 出版时间：October 2010
• 年：2010
• 卷：157
• 期：4
• 页码：653-657
• 全文大小：179 K

文摘

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.