Gene-Gene-Sex Interaction in Cytokine Gene Polymorphisms Revealed by Serum Interferon Alpha Phenotype in Juvenile Dermatomyositis
Gene-Gene-Sex Interaction in Cytokine Gene Polymorphisms Revealed by Serum Interferon Alpha Phenotype in Juvenile Dermatomyositis
复制标题
DOI：
10.1016/j.jpeds.2010.04.034
复制
发表时间：
2010-10-01
影响因子：
5.1
通讯作者：
Pachman, Lauren M.
中科院分区：
文献类型：
--
作者：
Niewold, Timothy B.;Kariuki, Silvia N.;Pachman, Lauren M.
目的检测青少年皮肌炎（JDM）患者血清干扰素α (ifn - α)高水平相关基因多态性，并探讨相关多态性之间的相互作用。研究设计对85名确诊/可能患有JDM的欧洲血统儿童进行了研究。在73名JDM儿童验证队列中，对12名未经治疗的新诊断JDM患者中与高ifn - α水平相关的选定遗传多态性进行基因分型，并分析基因-基因和基因-性别相互作用。结果携带骨桥蛋白（OPN） rs28357094G和肿瘤坏死因子α (tnf - α)-308 A等位基因的新诊断JDM患儿未经治疗后血清ifn - α水平显著升高。在验证队列中对这2种多态性进行基因分型，OPN rs28357094G等位基因在女性JDM患者中更为常见（优势比= 3.97,P = 0.012）。与男性tnf - α - 308a携带者相比，该OPN等位基因在女性tnf - α - 308a携带者中最富集（优势比>9.0;P = 7.2 × 10(-3)）。结论这些数据支持JDM中OPN和tnf - α启动子区域之间复杂的基因-基因-性别相互作用，在JDM中定义了高血清ifn - α亚群。这表明在患有JDM的女性受试者中，OPN和tnf - α基因座之间存在致病协同作用，这可能是女孩中该病发病率增加的部分原因。[J]儿科杂志2010；57:653- 57。
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 = 7.2 x 10(-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. (J Pediatr 2010;157:653-7).