title: STAT1 single nucleotide polymorphisms and susceptibility to immune thrombocytopenia.
abstract: 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 STAT1 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 STAT1 gene: rs10208033, rs12693591, and rs1467199. There is a statistically significant difference in STAT1 rs1467199 allele frequencies with comparison of each of the four clinical subgroups of ITP patients to the normal controls (p = 0.0432). Also, newly diagnosed ITP patients and chronic ITP patients demonstrate significant different genotypes (χ(2 )= 8.511, p = 0.0142) and allelic frequency (p = 0.0055). Although a positive STAT1 rs1467199 genotype subgroups to the STAT1 mRNA expression level cannot be established, there is a weak correlation between STAT1 mRNA level and the activity ratio of Type 1 T helper lymphocyte and Type 2 T helper lymphocyte (Th1/Th2 ratio) (p = 0.0544); correlation with IFN-γ alone did not reach statistical significance (p = 0.1715). The findings in our study suggest that STAT1 rs1467199 SNP plays a potential role in the IFN-γ dependent development of autoimmunity in children with ITP. The important clinical implication of STAT1 SNPs testing as a predictor of pediatric chronic ITP will be validated in future molecular and protein functional analysis.
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, Capital Medical University , Beijing , China .
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Guo
authors.forename: Jingyao
authors.initials: J
authors.lastname: Ma
authors.forename: Fuhong
authors.initials: F
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.forename: Shuguang
authors.initials: S
authors.lastname: Liu
authors.forename: Ami
authors.initials: A
authors.lastname: Wang
authors.forename: Runhui
authors.initials: R
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000483:Alleles; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor
keywords: Children; IFN-γ; STAT1; immune thrombocytopenia; single nucleotide polymorphism