STAT1 single nucleotide polymorphisms and susceptibility to immune thrombocytopenia. (August 2015)

• Record Type: Journal Article
• Authors: Chen, Zhenping; Guo, Zhenxing; Ma, Jingyao; Liu, Fuhong; Gao, Chao; Liu, Shuguang; Wang, Ami; Wu, Runhui
• Is Part Of: Autoimmunity. Volume 48:Number 5(2015)
• Page Start: 305
• Page End: 312
• Publication Date: 2015-08
• Subjects: Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; 571.973
• DOI: 10.3109/08916934.2015.1016218
• Languages: English
• ISSNs: 0891-6934

Abstract

<abstract> <title>Abstract</title> <p>Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder. One of the key mediators of IFN-γ signaling is the signal transducer and activator of transcription 1 protein (STAT1). We evaluated the relationship between <italic>STAT1</italic> gene single nucleotide polymorphisms (SNPs) and the associated risk of ITP in a prospective case–control study. A total of 548 children were recruited: 328 children with ITP and 220 healthy children as sex- and age-matched normal controls. The Sequenom MassArray system (Sequenom, San Diego, CA) was used to detect three SNPs genotypes in the <italic>STAT1</italic> gene: rs10208033, rs12693591, and rs1467199. There is a statistically significant difference in <italic>STAT1</italic> rs1467199 allele frequencies with comparison of each of the four clinical subgroups of ITP patients to the normal controls (<italic>p</italic> = 0.0432). Also, newly diagnosed ITP patients and chronic ITP patients demonstrate significant different genotypes (<italic>χ</italic><sup>2 </sup>= 8.511, <italic>p</italic> = 0.0142) and allelic frequency (<italic>p</italic> = 0.0055). Although a positive <italic>STAT1</italic> rs1467199 genotype subgroups to the <italic>STAT1</italic> mRNA expression level cannot be established, there is a weak correlation between <italic>STAT1</italic> mRNA level and the activity ratio of Type 1 T helper lymphocyte and Type 2 T helper lymphocyte (Th1/Th2 ratio) (<italic>p</italic> = 0.0544); correlation with IFN-γ alone did not reach statistical significance (<italic>p</italic> = 0.1715). The findings in our study suggest that <italic>STAT1</italic> rs1467199 SNP plays a potential role in the IFN-γ dependent development of autoimmunity in children with ITP. The important clinical implication of <italic>STAT1</italic> SNPs testing as a predictor of pediatric chronic ITP will be validated in future molecular and protein functional analysis.</p> </abstract>