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KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis susceptibility

2017; Impact Journals LLC; Volume: 8; Issue: 56 Linguagem: Inglês

10.18632/oncotarget.20727

1949-2553

Raffaella Cascella, Claudia Strafella, Michele Ragazzo, L. Manzo, Gaetana Costanza, John Bowes, Ulrike Hüffmeier, Saverio Potenza, Federica Sangiuolo, André Reis, Anne Barton, Giuseppe Novelli, Augusto Orlandi, Emiliano Giardina,

Spondyloarthritis Studies and Treatments

// Raffaella Cascella 1, 2, * , Claudia Strafella 3, 4, * , Michele Ragazzo 1, 5 , Laura Manzo 3, 4 , Gaetana Costanza 6 , John Bowes 7 , Ulrike Hüffmeier 8 , Saverio Potenza 3 , Federica Sangiuolo 3 , André Reis 8 , Anne Barton 7, 9 , Giuseppe Novelli 3 , Augusto Orlandi 10 and Emiliano Giardina 1, 3 1 Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, Rome, Italy 2 Department of Chemical Pharmaceutical and Biomolecular Technologies, Catholic University "Our Lady of Good Counsel" Laprakë, Rruga Dritan Hoxha, Tirana, Albania 3 Department of Biomedicine and Prevention, "Tor Vergata" University, Rome, Italy 4 Emotest Laboratory, Pozzuoli, Italy 5 Department of Medical Science, Catholic University "Our Lady of Good Counsel" Laprakë, Rruga Dritan Hoxha, Tirana, Albania 6 Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy 7 Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester, UK 8 Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany 9 NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester Academy of Health Sciences, Manchester, UK 10 Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Italy, Tor Vergata University Hospital, Rome, Italy * These authors have contributed equally to this work Correspondence to: Raffaella Cascella, email: raffaellacascella@virgilio.it Keywords: psoriatic arthritis, susceptibility, bone metabolism, 5q31 locus, linkage disequilibrium Received: June 22, 2017 Accepted: August 06, 2017 Published: September 08, 2017 ABSTRACT To date, the genes associated with Psoriatic Arthritis (PsA) are principally involved in inflammation, immune response and epidermal differentiation, without any information about the relationship between disease and bone metabolism genes. Our work was focused on 5q31 locus, which contains several genetic variants significantly associated with PsA. The study involved 1526 subjects (500 PsA, 426 PsV, 600 controls). The region was evaluated by selecting and genotyping the SNPs of interest by Real Time PCR and direct sequencing. The results were subjected to biostatistic and bioinformatic analysis. The case-control study highlighted a significant association between KIF3A/IL-4 and PsA, but not with PsV (Psoriasis Vulgaris) patients. In addition, the haplotype analysis revealed two haplotypes significantly associated with PsA susceptibility. The Linkage Disequilibrium (LD) study showed the presence of a specific block in high LD within 132,692,628-132,737,638 bp of 5q31, giving additional evidence of specific association of the 5q31 region in PsA patients. Moreover, KIF3A expression was assessed by immunohistochemistry assays which showed a marked and significant difference of KIF3A expression between pathological and normal tissues. Our analysis described KIF3A and IL-4 as novel susceptibility genes for PsA, suggesting a clear implication of bone metabolism genes in the disease etiopathogenesis.