PTPN22 gene polymorphism as a genetic risk factor for primary immune thrombocytopenia in Egyptian children

ABSTRACT

Objectives

Several genetic and non-genetic risk factors are implicated in the etiology and pathogenesis of primary immune thrombocytopenia (ITP). Protein tyrosine phosphatase non-receptor 22 gene (PTPN22) plays an important role in regulation of signal transduction through the T-cell receptors. PTPN22 1858 C > T single nucleotide polymorphism was reported to be associated with increased risk of autoimmune diseases. There are very few studies investigating the role of PTPN22(SNP) 1858 C > T in childhood ITP.

Methods

This case-control study was designed for assessing the contribution of PTPN22 1858 C > T polymorphism to the risk of ITP in Egyptian children. Eighty children with newly diagnosed ITP were recruited from pediatric hematology out-patient clinic. Also, eighty age and sex-matched healthy children were enrolled as a control group. PTPN22 1858 C/T SNP gene polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

Frequency of PTPN22 1858 C/T genotypes CT, CC, and TT were 32.5,55, and 12.5% in patients versus 10, 90, and 0% in controls (p < 0.05).TT genotype was significantly associated with higher risk of ITP (OR = 17.8(0.94–333.35), 95% CI, and P = 0.02).

Conclusion

PTPN22 gene polymorphism may play a pivotal role in genetic predisposition to ITP and disease progress in Egyptian children.

KEYWORDS:

• PTPN22
• gene
• polymorphism
• pediatric ITP
• immune thrombocytopenia

Expert opinion

Despite major research efforts, the pathophysiology of ITP is not fully understood. Many researchers highlight the contribution of the immune system in the pathogenesis of this disease. PTPN22 (1p13) is a protein that regulates the immune system responses, involved in distinguishing between self-antigens and non-self-antigens by lymphocytes. It has been reported that polymorphism 1858C>T in the gene encoding for PTPN22 protein prevents PTPN22 binding to signaling molecules in B-cell receptor and hence elevates the risk of developing autoimmune disorders like ITP through an unknown mechanism.

Acknowledgments

All authors of the study acknowledge and feel thankful for all study participants for their unlimited cooperation.

Author contributions

M.H., M.Z., and T.H. contributed to the design and performance of the research. E.A., S.E. and M.F. recruited pediatric patients and collected their data. A.F and N.M. performed the laboratory part of this work. All authors participated in data analysis, performed the statistics, and wrote the paper. M.Z. submitted the final manuscripts.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.