PMID- 33937970 OWN - NLM STAT- MEDLINE DCOM- 20211231 LR - 20211231 IS - 1179-2000 (Electronic) IS - 1177-1062 (Linking) VI - 25 IP - 4 DP - 2021 Jul TI - Serum Levels of miR-146a in Patients with Psoriasis. PG - 475-485 LID - 10.1007/s40291-021-00531-9 [doi] AB - 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. FAU - Leal, Barbara AU - Leal B AD - UMIB, Instituto de Ciencias Biomedicas Abel Salazar [ICBAS], Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. AD - Lab. Imunogenetica, DPIM, ICBAS-UPorto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. FAU - Carvalho, Claudia AU - Carvalho C AD - UMIB, Instituto de Ciencias Biomedicas Abel Salazar [ICBAS], Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. AD - Lab. Imunogenetica, DPIM, ICBAS-UPorto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. FAU - Ferreira, Ana Marta AU - Ferreira AM AD - UMIB, Instituto de Ciencias Biomedicas Abel Salazar [ICBAS], Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. AD - Lab. Imunogenetica, DPIM, ICBAS-UPorto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. FAU - Nogueira, Miguel AU - Nogueira M AD - Dermatology Department, Centro Hospitalar Universitario do Porto, Largo Prof. Abel Salazar, 4099-003, Porto, Portugal. FAU - Bras, Sandra AU - Bras S AD - Lab. Imunogenetica, DPIM, ICBAS-UPorto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. FAU - Silva, Berta M AU - Silva BM AD - UMIB, Instituto de Ciencias Biomedicas Abel Salazar [ICBAS], Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. AD - Lab. Imunogenetica, DPIM, ICBAS-UPorto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. FAU - Selores, Manuela AU - Selores M AD - UMIB, Instituto de Ciencias Biomedicas Abel Salazar [ICBAS], Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. AD - Dermatology Department, Centro Hospitalar Universitario do Porto, Largo Prof. Abel Salazar, 4099-003, Porto, Portugal. FAU - Costa, Paulo P AU - Costa PP AD - UMIB, Instituto de Ciencias Biomedicas Abel Salazar [ICBAS], Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. AD - Lab. Imunogenetica, DPIM, ICBAS-UPorto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. AD - Departamento de Genetica, Instituto Nacional de Saude Dr. Ricardo Jorge-Porto, Rua Pedro Nunes, n. masculine 88, 4099-032, Porto, Portugal. FAU - Torres, Tiago AU - Torres T AUID- ORCID: 0000-0003-0404-0870 AD - UMIB, Instituto de Ciencias Biomedicas Abel Salazar [ICBAS], Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal. torres.tiago@outlook.com. AD - Dermatology Department, Centro Hospitalar Universitario do Porto, Largo Prof. Abel Salazar, 4099-003, Porto, Portugal. torres.tiago@outlook.com. AD - Dermatology Research Unit, Centro Hospitalar Universitario do Porto, Largo Prof. Abel Salazar, 4099-003, Porto, Portugal. torres.tiago@outlook.com. LA - eng PT - Journal Article DEP - 20210502 PL - New Zealand TA - Mol Diagn Ther JT - Molecular diagnosis & therapy JID - 101264260 RN - 0 (HLA-C Antigens) RN - 0 (HLA-C*06:02 antigen) RN - 0 (MIRN146 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Adult MH - Aged MH - Case-Control Studies MH - Female MH - Genetic Predisposition to Disease MH - Genotyping Techniques MH - HLA-C Antigens/genetics MH - Humans MH - Male MH - MicroRNAs/*blood MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Portugal MH - Psoriasis/blood/*genetics MH - *Up-Regulation MH - Young Adult EDAT- 2021/05/04 06:00 MHDA- 2022/01/01 06:00 CRDT- 2021/05/03 06:32 PHST- 2021/04/17 00:00 [accepted] PHST- 2021/05/04 06:00 [pubmed] PHST- 2022/01/01 06:00 [medline] PHST- 2021/05/03 06:32 [entrez] AID - 10.1007/s40291-021-00531-9 [pii] AID - 10.1007/s40291-021-00531-9 [doi] PST - ppublish SO - Mol Diagn Ther. 2021 Jul;25(4):475-485. doi: 10.1007/s40291-021-00531-9. Epub 2021 May 2.