Abstract
Psoriasis (Ps) and Psoriatic Arthritis (PsA) are characterized by a multifactorial etiology, involving genetic and environmental factors. The present study aimed to investigate polymorphisms (SNPs) within genes involved in extracellular matrix and cell homeostasis and microRNA genes as susceptibility biomarkers for Ps and PsA. Bioinformatic analysis on public RNA-seq data allowed for selection of rs12488457 (A/C, COL6A5), rs13081855 (G/T, COL8A1), rs3812111 (A/T, COL10A1) and rs2910164 (C/G, MIR146A) as candidate biomarkers. These polymorphisms were analyzed by Real-Time PCR in a cohort of 1417 Italian patients (393 Ps, 424 PsA, 600 controls). Statistical and bioinformatic tools were utilized for assessing the genetic association and predicting the effects of the selected SNPs. rs12488457, rs13081855 and rs2910164 were significantly associated with both Ps (p = 1.39 × 10−8, p = 4.52 × 10−4, p = 0.04, respectively) and PsA (p = 5.12 × 10−5, p = 1.19 × 10−6, p = 0.01, respectively). rs3812111, instead, was associated only with PsA (p = 0.005). Bioinformatic analysis revealed common and differential biological pathways involved in Ps and PsA. COL6A5 and COL8A1 take part in the proliferation and angiogenic pathways which are altered in Ps/PsA and contribute to inflammation together with MIR146A. On the other hand, the exclusive association of COL10A1 with PsA highlighted the specific involvement of bone metabolism in PsA.
Highlights
Psoriasis (Ps) and Psoriatic Arthritis (PsA) are chronic, inflammatory, immune-mediated pathologies characterized by a multifactorial etiology [1,2]
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This study investigated the single nucleotide polymorphisms (SNPs) rs12488457 (A/C, COL6A5), rs13081855 (G/T, COL8A1), rs3812111 (A/T, COL10A1) and rs2910164 (C/G, MIR146A) as potential susceptibility biomarkers for Ps and/or PsA
Summary
Psoriasis (Ps) and Psoriatic Arthritis (PsA) are chronic, inflammatory, immune-mediated pathologies characterized by a multifactorial etiology [1,2]. We selected these SNPs considering the literature and our own laboratory works, which have previously investigated them as susceptibility factors for Age-related Macular Degeneration (AMD) and Atopic Eczema (AE) Both AMD and AE are characterized by the alteration of immune/inflammatory pathways similar to Ps and PsA [13,14]. A secondary aim of the study was the investigation of polymorphisms in miRNA-encoding genes, which may be associated with the susceptibility to Ps and/or PsA through the epigenetic regulation of inflammatory and cell proliferation pathways On this subject, a polymorphism (rs2910164, C/G) located in the MicroRNA 146a (MIR146A, 5q33.3) gene was selected as a potential susceptibility biomarker in Ps and/or PsA. Sci. 2019, 20, x FOR PEER REVIEW (miRa-s14a6ap-o5tpenatinadl smusicRe-p1t4ib6iali-t3ypb)i,owmhairckherairne kPns oawndn/otro PtasAke. pInarftacitn, itnhfle aMmIRm1a4t6oArygeannedccoedlel sprfoorliferation pathhwoamyosnyamndouhs amveiRbNeAens f(mouiRn-d146aas-s5opciaantedd mwiRit-h14s6eav-3epr)a, l wmhuiclhtifaarcetokrinaolwdnisotordtearkse (spuarcth inas cancer, Alzhimenifumllatemifram’cstaoDtroiirasyleadasinesdo, radnceedrllsA(psMruocDlhif)e.arGsatiicvoanennceptrah,tehAswlezahdyeasitmaa,enrtd’hsehDraisvs2ee9a1sbe0e,1e6ann4dfvoaAurnMiadDnta).shsGaoiscvibaetneeedtnhewsseieltehdcatseteadv, ectrhoaenl sidering that irts2h9a1s01b6e4envafroiaunntdhtaos cboenentrisbeuletcetetdo tchoensseidderiisnogrdthearst [i1t 5h]a. s been found to contribute to these disorders [15]
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