title: Role of PTPN22 and CSK gene polymorphisms as predictors of susceptibility and clinical heterogeneity in patients with Henoch-Schönlein purpura (IgA vasculitis).
abstract: BACKGROUND
  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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  No 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.
  
  
  CONCLUSIONS
  Our results do not support association between PTPN22/CSK and HSP.
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. rlopezmejias78@gmail.com.
authors.forename: Raquel
authors.initials: R
authors.lastname: López-Mejías
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. fernandagenre@gmail.com.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Genre
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. sara.r.mtz@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Remuzgo-Martínez
authors.affiliation: Department of Medicine, Hospital Universitario San Cecilio, Calle Dr. Oloriz, 16, 18012, Granada, Spain. belensev@hotmail.com.
authors.forename: Belén Sevilla
authors.initials: BS
authors.lastname: Pérez
authors.affiliation: Rheumatology Department, Hospital Universitario La Princesa, IIS-Princesa, Calle Diego de León, 62, 28006, Madrid, Spain. scastas@gmail.com.
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.affiliation: Epidemiology and Computational Biology Department, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVAL, Avenida Cardenal Herrera Oria, s/n, 39011, Santander, Spain. llorcaj@unican.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.affiliation: Department of Medicine, Hospital Universitario San Cecilio, Calle Dr. Oloriz, 16, 18012, Granada, Spain. nortego@gmail.com.
authors.forename: Norberto
authors.initials: N
authors.lastname: Ortego-Centeno
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. b.ubilla.garcia@gmail.com.
authors.forename: Begoña
authors.initials: B
authors.lastname: Ubilla
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. necover23@yahoo.es.
authors.forename: Verónica
authors.initials: V
authors.lastname: Mijares
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. alicantrino@hotmail.com.
authors.forename: Trinitario
authors.initials: T
authors.lastname: Pina
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. fiorelfa@hotmail.com.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Calvo-Río
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. npalmouu@gmail.com.
authors.forename: Natalia
authors.initials: N
authors.lastname: Palmou
authors.affiliation: Division of Rheumatology, Hospital Universitario Lucus Augusti, Calle Dr. Ochoa, s/n, 27004, Lugo, Spain. jose.alberto.miranda.filloy@sergas.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Miranda-Filloy
authors.affiliation: Nephrology Department, Hospital Universitario San Cecilio, Calle Dr. Oloriz, 16, 18012, Granada, Spain. antonionavasparejo@gmail.com.
authors.forename: Antonio Navas
authors.initials: AN
authors.lastname: Parejo
authors.affiliation: Dermatology Department, Hospital Universitario La Princesa, IIS-Princesa, Calle Diego de León, 62, 28006, Madrid, Spain. dargilad@hotmail.com.
authors.forename: Diego
authors.initials: D
authors.lastname: Argila
authors.affiliation: Dermatology Department, Hospital Universitario La Princesa, IIS-Princesa, Calle Diego de León, 62, 28006, Madrid, Spain. jsanchezperez@aedv.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Sánchez-Pérez
authors.affiliation: Rheumatology Department, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013, Sevilla, Spain. cybereste@hotmail.com.
authors.forename: Esteban
authors.initials: E
authors.lastname: Rubio
authors.affiliation: Rheumatology Department, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot, s/n, 41013, Sevilla, Spain. manuelleonluque@gmail.com.
authors.forename: Manuel León
authors.initials: ML
authors.lastname: Luque
authors.affiliation: Rheumatology Department, Hospital Universitario de Basurto, Avenida de Montevideo, 18, 48013, Bilbao, Spain. juanmaria.blancomadrigal@osakidetza.net.
authors.forename: Juan María
authors.initials: JM
authors.lastname: Blanco-Madrigal
authors.affiliation: Rheumatology Department, Hospital Universitario de Basurto, Avenida de Montevideo, 18, 48013, Bilbao, Spain. evagalindez@gmail.com.
authors.forename: Eva
authors.initials: E
authors.lastname: Galíndez-Aguirregoikoa
authors.affiliation: Immunology Department, Hospital Universitario Marqués de Valdecilla, Avenida de Valdecilla, s/n, 39008, Santander, Spain. jgocejo@humv.es.
authors.forename: J Gonzalo
authors.initials: JG
authors.lastname: Ocejo-Vinyals
authors.affiliation: Institute of Parasitology and Biomedicine López-Neyra, CSIC, Avenida del Conocimiento, s/n, 18016, Granada, Spain. martin@ipb.csic.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. rblanco@humv.es.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, Avenida de Valdecilla, s/n, 39008, Santander, Spain. miguelaggay@hotmail.com.|Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa. miguelaggay@hotmail.com.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
mesh_terms: D000328:Adult; D000081247:CSK Tyrosine-Protein Kinase; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D011695:IgA Vasculitis / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013030:Spain; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22