Perfil genético da doença psoriásica: associação dos antígenos leucocitários humanos (HLA) classe I e classe II e dos polimorfismos de nucleotídeo único (SNPs) do TNF-alfa (rs361525), IL17RA (rs4819554) e do Act1/TRAF (rs33980500) em pacientes do Rio de Janeiro

• Ano de defesa: 2025
• Autor(a) principal: Sampaio, Ana Luisa
• Outros Autores: [e-mail]
• Orientador(a): Abulafia, Luna Azulay
• Banca de defesa: Carneiro, Sueli Coelho da Silva , Pôrto, Luis Cristóvão de Moraes Sobrino , Pinto, Jane Marcy Neffá , Magalhães, Renata Ferreira
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Médicas
• Departamento: Centro Biomédico::Faculdade de Ciências Médicas
• País: Brasil
• Palavras-chave em Português: Psoríase – Genética; Antígenos leucocitários humanos (HLA); Polimorfismos genéticos; Polimorfismos de nucleotideo único (SNP); Medicina de precisão; Polimorfismo (Genética); Predisposição genética para doença
• Palavras-chave em Inglês: Psoriasis; Human leukocyte antigens (HLA); Genetic polymorphisms; Single nucleotide polymorphisms (SNP); Precision medicine
• Área do conhecimento CNPq: CIENCIAS DA SAUDE::MEDICINA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/25464

This study investigates associations between Human Leukocyte Antigen (HLA) alleles and single nucleotide polymorphisms (SNPs) with psoriasis in a highly admixed cohort from Southeastern Brazil. Using a case–control design, 144 patients and 720 controls were genotyped for HLA, and SNPs in IL17RA (rs4819554), TNF-238 (rs361525), and ACT1/TRAF3 (rs33980500) were analyzed in a matched subset (121 cases and 121 controls). Disease severity was classified using PASI scores, incorporating prior or current use of systemic therapy as a marker of moderate to severe disease. Stratification was also performed according to age at onset. Hardy–Weinberg equilibrium, linkage disequilibrium, Bonferroni correction, and Principal Component Analysis (PCA) were applied. A robust association between HLA-C*06:02g and disease susceptibility was confirmed (OR = 2.13; p = 0.0001; pC = 0.007), with no relationship to disease severity or age at onset. Initial risk alleles were identified in both class I and II loci; however, after Bonferroni correction, only C*06:02g remained significant. A novel protective effect of DRB1*15:03g was observed (pC = 0.027). Phenotypic analysis revealed a higher frequency of A*34:02g and B*50:01g in mild disease, whereas DRB1*01:01g occurred exclusively in moderate to severe disease. Regarding age at onset, late-onset psoriasis (>30 years) was associated with A*23:01g, A*30:01g, B*15:03, and DQB1*03:03g, while early-onset disease was linked to B*44:03g and C*07:02g (the latter being five times more frequent in younger patients). PCA revealed clusters consistent with risk and protective profiles, with DQB1 positioned at an extreme pole, while the DRB1~DQB1 linkage disequilibrium pattern remained similar between cases and controls. The SNPs analyzed did not show significant associations with disease susceptibility or severity, although a trend was noted for the IL17RA A/G genotype in moderate to severe disease. These findings demonstrate that the genetic architecture of psoriasis in Brazil combines the classical C*06:02g signal with protective class II signatures, phenotype modulators, and certain class I haplotypes, outlining a distinctive pattern in this admixed population.