Bárbara Leal1,2, Cláudia Carvalho1,2, Ana Marta Ferreira1,2, Miguel Nogueira3, Sandra Brás2, Berta M Silva1,2, Manuela Selores1,3, Paulo P Costa1,2,4, Tiago Torres5,6,7. 1. UMIB, Instituto de Ciências Biomédicas Abel Salazar [ICBAS], Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. 2. Lab. Imunogenética, DPIM, ICBAS-UPorto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. 3. Dermatology Department, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar, 4099-003, Porto, Portugal. 4. Departamento de Genética, Instituto Nacional de Saúde Dr. Ricardo Jorge-Porto, Rua Pedro Nunes, n.º 88, 4099-032, Porto, Portugal. 5. UMIB, Instituto de Ciências Biomédicas Abel Salazar [ICBAS], Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. torres.tiago@outlook.com. 6. Dermatology Department, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar, 4099-003, Porto, Portugal. torres.tiago@outlook.com. 7. Dermatology Research Unit, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar, 4099-003, Porto, Portugal. torres.tiago@outlook.com.
Abstract
BACKGROUND: Psoriasis is an immune-mediated disease with interactions between genetic and environmental factors. An increasing number of studies are demonstrating the importance of microRNAs (miRNAs) in the pathogenesis of psoriasis. miR-146a, a dominant negative regulator of inflammation, has been consistently reported as overexpressed in the skin and peripheral blood mononuclear cells (PBMCs) of patients with psoriasis. Expression and/or function of this miRNA is highly influenced by genetic variations, some of which have already been associated with susceptibility to psoriasis. OBJECTIVE: We sought to study the importance of miR-146a in patients with moderate-to-severe psoriasis and to understand the impact of rs57095329 and rs2910164 polymorphisms in a psoriatic Portuguese population. METHODS: miR-146a circulating levels were quantified using molecular biology techniques in 99 patients with moderate-to-severe psoriasis (35 female, 64 male; age 47.4 ± 10.9 years) and 78 healthy individuals (52 female, 26 male; age 42.4 ± 10.1 years). miRNA expression was correlated with clinicopathological features as well as with genetic data such as the presence of human leukocyte antigen (HLA)-C*0602 allele and two miR-146a polymorphisms (rs2910164 and rs57095329). RESULTS: miR-146a serum levels were 3.7-fold higher in patients with psoriasis than in controls (p < 0.0001, area under the curve [AUC] 0.75; 95% confidence interval [CI] 0.66-0.83). Of note, miR-146a circulating levels positively correlated with Psoriasis Area and Severity Index (p < 0.05) and body surface area (p < 0.05) indexes. No variations in miR-146a levels were observed with rs2910164 and rs57095329 genotypes. CONCLUSION: Circulating miR-146a levels were upregulated in patients with psoriasis, especially in those with active disease. To the best of our knowledge, this is the largest study with a homogenous psoriasis population, and our data could shed light on the pathogenesis of psoriasis, paving the way for new avenues for disease treatment.
BACKGROUND: Psoriasis is an immune-mediated disease with interactions between genetic and environmental factors. An increasing number of studies are demonstrating the importance of microRNAs (miRNAs) in the pathogenesis of psoriasis. miR-146a, a dominant negative regulator of inflammation, has been consistently reported as overexpressed in the skin and peripheral blood mononuclear cells (PBMCs) of patients with psoriasis. Expression and/or function of this miRNA is highly influenced by genetic variations, some of which have already been associated with susceptibility to psoriasis. OBJECTIVE: We sought to study the importance of miR-146a in patients with moderate-to-severe psoriasis and to understand the impact of rs57095329 and rs2910164 polymorphisms in a psoriatic Portuguese population. METHODS: miR-146a circulating levels were quantified using molecular biology techniques in 99 patients with moderate-to-severe psoriasis (35 female, 64 male; age 47.4 ± 10.9 years) and 78 healthy individuals (52 female, 26 male; age 42.4 ± 10.1 years). miRNA expression was correlated with clinicopathological features as well as with genetic data such as the presence of human leukocyte antigen (HLA)-C*0602 allele and two miR-146a polymorphisms (rs2910164 and rs57095329). RESULTS: miR-146a serum levels were 3.7-fold higher in patients with psoriasis than in controls (p < 0.0001, area under the curve [AUC] 0.75; 95% confidence interval [CI] 0.66-0.83). Of note, miR-146a circulating levels positively correlated with Psoriasis Area and Severity Index (p < 0.05) and body surface area (p < 0.05) indexes. No variations in miR-146a levels were observed with rs2910164 and rs57095329 genotypes. CONCLUSION: Circulating miR-146a levels were upregulated in patients with psoriasis, especially in those with active disease. To the best of our knowledge, this is the largest study with a homogenous psoriasis population, and our data could shed light on the pathogenesis of psoriasis, paving the way for new avenues for disease treatment.
Authors: Jacqueline E Greb; Ari M Goldminz; James T Elder; Mark G Lebwohl; Dafna D Gladman; Jashin J Wu; Nehal N Mehta; Andrew Y Finlay; Alice B Gottlieb Journal: Nat Rev Dis Primers Date: 2016-11-24 Impact factor: 52.329
Authors: Jason E Hawkes; Giang Huong Nguyen; Mayumi Fujita; Scott R Florell; Kristina Callis Duffin; Gerald G Krueger; Ryan M O'Connell Journal: J Invest Dermatol Date: 2016-02 Impact factor: 8.551