Role of PTPN22 and CSK gene polymorphisms as predictors of susceptibility and clinical heterogeneity in patients with Henoch-Schönlein purpura (IgA vasculitis).

Raquel López‐Mejías ,Santos Castañeda,Esteban Rubio,Belén Sevilla Pérez,Antonio Navas Parejo,Fernanda Genre,Trinitario Pina,Manuel León Luque,Javier Llorca,Begoña Ubilla,Natalia Palmou,Eva Galíndez-Aguirregoikoa,Juan María Blanco-Madrigal,Verónica Mijares,José A Miranda‐Filloy ,D De Argila ,Javier Gonzalo Ocejo-Vinyals ,V Calvo-Río ,R Blanco ,Javier Martı́n ,Sara Remuzgo‐Martínez ,Norbérto Ortego-Centeno ,Javier Sánchez‐Pérez ,Miguel A González‐Gay

doi:10.1186/s13075-015-0796-x

Abstract

IntroductionTo determine whether the PTPN22 (protein tyrosine phosphatase nonreceptor 22)/CSK (c-src tyrosine kinase) pathway is implicated in the susceptibility and clinical heterogeneity of Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies.MethodsA set of 329 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria and 515 sex and ethnically matched controls were recruited in this study. Two well-known CSK (CSK rs34933034 and CSK rs1378942) and two functional PTPN22 (PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q)) polymorphisms, previously associated with autoimmunity, were genotyped with TaqMan single nucleotide polymorphism (SNP) genotyping assays.ResultsNo significant differences in the genotype and allele frequencies between HSP patients and controls were observed when the CSK rs34933034, CSK rs1378942, PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q) polymorphisms were analyzed independently. In keeping with this observation, no significant differences were found when we assessed these polymorphisms combined conforming haplotypes. In addition, there were no differences in the allele or genotype frequencies when HSP patients were stratified according the age at disease onset, sex, presence of arthralgia/arthritis, nephritis or gastrointestinal manifestations.ConclusionsOur results do not support association between PTPN22/CSK and HSP.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0796-x) contains supplementary material, which is available to authorized users.

Highlights

To determine whether the protein tyrosine phosphatase nonreceptor 22 (PTPN22)/CSK (c-src tyrosine kinase) pathway is implicated in the susceptibility and clinical heterogeneity of Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies
Adults presenting with palpable purpura required the presence of other manifestations and, the exclusion of other vasculitis such as antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis was required in these cases
Differences in genotype and allele frequencies between HSP patients and controls The CSK rs34933034, CSK rs1378942, PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q) genotypes distribution were in Hardy-Weinberg equilibrium (Table 2) and for these four single nucleotide polymorphisms (SNPs) the genotyping success in HSP

Summary

Introduction

To determine whether the PTPN22 (protein tyrosine phosphatase nonreceptor 22)/CSK (c-src tyrosine kinase) pathway is implicated in the susceptibility and clinical heterogeneity of Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies. Henoch-Schönlein purpura (HSP), called immunoglobulin A (IgA) vasculitis, is a leukocytoclastic vasculitis characterized by IgA-dominant immune deposits involving mainly the skin as well as other tissues [1]. HSP often causes joint pain and gastrointestinal complications [2]. Renal manifestations constitute the most serious complications of HSP [2] and long-term morbidity and mortality in these patients are mainly due to renal involvement. The relevance of genetic variants in both susceptibility and HSP clinical heterogeneity has been demonstrated [3,4,5]

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