STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms influence the risk of developing juvenile idiopathic arthritis in Han Chinese patients.

Zhi-Dan Fan,Yi-Hong Guo,Ya-Yuan Zhang,Hui-Hui Ma,Hui Huang,Na Huang,Hai-Guo Yu,Fei-Fei Wang,Xiao-Qing Qian,Robert Lafrenie

doi:10.1371/journal.pone.0117389

Zhi-Dan Fan, Yi-Hong Guo + Show 8 more

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https://doi.org/10.1371/journal.pone.0117389

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Journal: PloS one	Publication Date: Mar 17, 2015
Citations: 17	License type: CC BY 4.0

Affiliation: Nanjing Children's Hospital, Nanjing Medical University

Abstract

Juvenile idiopathic arthritis (JIA) is a common autoimmune disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The protein tyrosine phosphatase nonreceptor 22 (PTPN22) and signal transducer and activator of transcription factor 4 (STAT4) have been recognized as susceptibility genes for numerous autoimmune diseases. Associations of STAT4 rs7574865 G/T and PTPN22 (rs2488457 G/C and rs2476601 C/T) polymorphisms with JIA have repeatedly been replicated in several Caucasian populations. The aim of this study was to investigate the influence of three polymorphisms mentioned above on the risk of developing JIA in Han Chinese patients. Genotyping was performed on a total of 137 Chinese patients with JIA (JIA group) and 150 sex and age frequency-matched healthy volunteers (Control group). The single-nucleotide polymorphisms (SNP) were determined by using direct sequencing of PCR-amplified products. There were significant differences of PTPN22 rs2488457 G/C and STAT4 rs7574865 G/T polymorphisms between both groups. However, no significant difference was observed in distribution frequencies of PTPN22 rs2476601 polymorphism. The association with the PTPN22 rs2488457 G/C polymorphism remained significant in the stratifications by age at onset, ANA status, splenomegaly, lymphadenectasis and involvement joints. As with the STAT4 rs7574865 G/T polymorphisms, the enthesitis-related arthritis and presence of hepatomegaly had strong effect on the association. Our data strengthen STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms as susceptibility factors for JIA.

Highlights

Juvenile idiopathic arthritis (JIA) is one of the most common autoimmune diseases with genetic background and characterized by chronic inflammation of one or more joints in children [1,2]
The rs2476601 single-nucleotide polymorphisms (SNP) is almost absent in Asian populations [10, 12] and virtually non-polymorphic in Han Chinese according to HapMap data, suggesting that if Protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with JIA in Chinese populations, it is likely to be via another potentially functional SNP
Allele and genotype frequencies for the PTPN22 SNPs and STAT4 SNP were in Hardy-Weinberg equilibriumin in both the JIA patients and controls (P>0.05)

Summary

Introduction

Juvenile idiopathic arthritis (JIA) is one of the most common autoimmune diseases with genetic background and characterized by chronic inflammation of one or more joints in children [1,2]. It is of unknown etiology with onset before 16 years of age [3]. The presence of a C-T substitution (rs2476601) in the 14th exon of PTPN22 gene, increases susceptibility to JIA in UK [8], Finnish [9] and Norwegian [10] populations, but presents no association in Greek [11] and Hungarian [2] patients. As RA shares similar clinical presentation and pathological features with JIA [8, 14], so the rs2488457 SNP may confer susceptibility to the development of rheumatic diseases

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