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Abstract
Cytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.
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1 Hospital Universitario Marqués de Valdecilla, Research Group On Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Division of Rheumatology, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262)
2 Hospital Universitario Marqués de Valdecilla, Research Group On Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Division of Rheumatology, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262); Hospital Universitario Marqués de Valdecilla, López Albo´ Post-Residency Programme, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262)
3 Universidad de Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), Epidemiology and Computational Biology Department, School of Medicine, Santander, Spain (GRID:grid.7821.c) (ISNI:0000 0004 1770 272X)
4 Hospital Universitario San Cecilio, Division of Paediatrics, Granada, Spain (GRID:grid.459499.c)
5 Universidad de Granada, Department of Medicine, Granada, Spain (GRID:grid.4489.1) (ISNI:0000000121678994)
6 Instituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, PTS Granada, Granada, Spain (GRID:grid.429021.c) (ISNI:0000 0004 1775 8774); Hospital Universitario Clínico San Cecilio, Instituto de Investigación Biosanitaria ibs.GRANADA, Systemic Autoimmune Disease Unit, Granada, Spain (GRID:grid.459499.c)
7 Hospital Universitario Marqués de Valdecilla, Division of Paediatrics, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262)
8 Hospital Universitario de Bellvitge, Division of Rheumatology, Barcelona, Spain (GRID:grid.411129.e) (ISNI:0000 0000 8836 0780)
9 Hospital Universitario Marqués de Valdecilla, IDIVAL-REDINREN, Division of Nephrology, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262)
10 Hospital Universitario Lucus Augusti, Division of Rheumatology, Lugo, Spain (GRID:grid.414792.d) (ISNI:0000 0004 0579 2350)
11 Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Division of Rheumatology, Oviedo, Spain (GRID:grid.411052.3) (ISNI:0000 0001 2176 9028)
12 Hospital Universitario Severo Ochoa, Division of Rheumatology, Madrid, Spain (GRID:grid.411361.0) (ISNI:0000 0001 0635 4617)
13 Hospital Universitario de La Princesa, Department of Dermatology, Madrid, Spain (GRID:grid.411251.2) (ISNI:0000 0004 1767 647X)
14 Hospital Universitario Virgen del Rocío, Department of Rheumatology, Sevilla, Spain (GRID:grid.411109.c) (ISNI:0000 0000 9542 1158)
15 Hospital Universitario de Basurto, Department of Rheumatology, Bilbao, Spain (GRID:grid.411109.c)
16 Hospital Clínico Universitario de Santiago, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago de Compostela, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945)
17 Instituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, PTS Granada, Granada, Spain (GRID:grid.429021.c) (ISNI:0000 0004 1775 8774)
18 Hospital Universitario de La Princesa, IIS-Princesa, Department of Rheumatology, Madrid, Spain (GRID:grid.411251.2) (ISNI:0000 0004 1767 647X)
19 Hospital Universitario Marqués de Valdecilla, Research Group On Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Division of Rheumatology, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262); Universidad de Cantabria, School of Medicine, Santander, Spain (GRID:grid.7821.c) (ISNI:0000 0004 1770 272X); University of the Witwatersrand, Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135)