SHORT COMMUNICATION

Frequency of TNFalpha, IL17RA, and Act1 Genetic Polymorphisms in a Population with Psoriasis Compared with Healthy Individuals: Results in a Multiracial Population in Rio de Janeiro, Brazil

Ana Luisa SAMPAIO1,2 symbol, Bruna ROMANA-SOUZA3* symbol, Haizza Cristina Cabral DE ALMEIDA MONTEIRO2 symbol, Camila Oliveira DA SILVA4 symbol and Luna AZULAY-ABULAFIA2 symbol

1Medical Science Post Graduate Program, Rio de Janeiro State University, Rio de Janeiro, Brazil, 2Dermatology Service, Pedro Ernesto University Hospital (HUPE), and Internal Medicine Department, Faculty of Medical Sciences, Rio de Janeiro State University, Rio de Janeiro, Brazil, 3Tissue Repair Laboratory, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil, and 4Tissue Repair and Histocompatibility Technological Core (Tixus), Rio de Janeiro State University, Rio de Janeiro, Brazil. *E-mail: romanabio@gmail.com

 

Citation: Acta Derm Venereol 2025; 105: adv42017. DOI: https://doi.org/10.2340/actadv.v105.42017.

Copyright: © 2025 The Author(s). Published by MJS Publishing, on behalf of the Society for Publication of Acta Dermato-Venereologica. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/).

Submitted: Sep 15, 2024. Accepted after revision: Feb 11, 2025. Published: Mar 7, 2025.

Competing interests and funding: The authors have no conflicts of interest to declare.
This work was supported by FAPERJ (Fundação do Amparo à Pesquisa do Estado do Rio de Janeiro – grant number E-26/202.683/2019) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico do Brasil – grant number 310885/2022. COS was recipient of a post-doctoral bursary form FAPERJ.

 

INTRODUCTION

Psoriasis is a chronic systemic inflammatory disease with genetic underpinnings, affecting approximately 2–3% of Caucasian Europeans (1) and an estimated 1.3% of Brazilians, with regional variability (2). The disease arises from dysregulation of innate and adaptive immune responses, with the Th17/Th23 axis playing a pivotal role in its pathogenesis (3, 4). Genetic predisposition is a significant determinant of disease risk and severity (5), often influencing treatment strategies based on metrics like the Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) (6). While psoriasis can manifest at any age, there are 2 notable peaks of incidence: in young people around 30 and above 60 years old (3).

Genome-wide studies have identified over 109 loci associated with psoriasis susceptibility (7). However, genetic variation among populations remains underexplored, particularly in Brazil’s diverse, multiracial context. In Rio de Janeiro, genetic influences include Native Amerindians, Iberian (Portuguese), and African descent, potentially affecting psoriasis profiles compared with Latin America.

HLA-C*06:02, which is linked to autoantigen recognition and inflammation, stands out as a major contributor (8). Similarly, the TNF-α gene, extensively studied for its role in immune regulation, contains promoter region mutations associated with psoriasis. Notably, specific SNPs, including TNF alleles – rs361525 (238G/A) and rs1800629 (308G/A) – influence its gene expression. The A allele of rs361525 has been implicated in increased risk of type 1 psoriasis (9), though findings have been inconsistent across studies (10). A Brazilian study conducted in 2010 found the -238G/G genotype to be more frequently associated with severe psoriasis (11). Polymorphisms in the IL17RA gene, which encodes the interleukin 17A receptor, have also been linked to a higher incidence of psoriasis in a Spanish population. These polymorphisms exhibit linkage disequilibrium with HLA-C*06 and are associated with improved response to certain therapies, such as TNF-α blockers (12). The Act1 gene, also known as TRAF3IP2 or CIKS, is essential for IL-17 receptor intracellular signalling within the NF-κB pathway, a key mediator of inflammation in psoriasis. A specific SNP, SNP-D10N (rs33980500), leads to hyperactivation of the Th17 inflammatory response (13) and is related to the disease in a Polish population (14).

In this study, we investigated 3 SNPs commonly associated with psoriasis pathophysiology in global populations, focusing on a mixed-race Brazilian cohort. These SNPs included rs361525 (A/G) in the TNF-α promoter region, rs4819554 (A/G) in the IL17RA gene, and rs33980500 (C/T) in the TRAF3 gene, which is involved in the NF-κB inflammatory cascade (Table I), the intracellular inflammatory pathway mediated by IL17. We examined their prevalence in healthy individuals and psoriatic patients, stratifying disease severity into mild or moderate-to-severe categories based on PASI ≥ 10 or current/previous systemic therapy and age of onset of the disease.

Table I. Demographic data and severity of psoriasis
Factor Control
(n=121)		 Psoriasis
(n=121)		 p-value
Sex
 Male 62 (49.6%) 63 (50.4%) NS
 Female 59 (50.4%) 58 (49.6%)
Age (years) at diagnostic onset 26 [17–58] 50 [39–82]
31 [5–74]*		 <0.001
<0.001
Colour/race auto-declaration
 White 60 (58.25%) 43 (41.75%) NS
 Multiracial 47 (45.19%) 57 (54.81%)
 Black 14 (40%) 21 (60%)
Severity of psoriasis
 Mild psoriasis – 23 (19%)
 Moderate to severe psoriasis – 98 (81%)
Healthy controls were volunteers with no history or current diagnosis of psoriasis or other inflammatory skin diseases, as well as no psychiatric disorders, intellectual disabilities, or visible skin conditions. Patients were recruited from the Dermatology Outpatient Clinics of Pedro Ernesto University Hospital (HUPE) or Piquet Carneiro University Policlinic (PPC), with selection criteria including a disease duration of more than 10 years and the absence of psychiatric disorders or intellectual impairments. Data are expressed as frequency or mean [min–max]. NS: non-significant, a p-value of less than 0.05 was considered statistically significant.

MATERIALS AND METHODS

We recruited 121 plaque psoriasis patients (81% with PASI ≥10) and 121 healthy controls matched for sex and ethnicity (Table I). Informed consent was obtained, and the study was approved by the Research Ethics Committee of Pedro Ernesto University Hospital (CAAE: 31055720.9.0000.5259). Genomic DNA was extracted, and SNPs were genotyped using TaqMan probes (Table SI). Statistical analysis included Hardy–Weinberg Equilibrium (HWE) testing, χ2 tests for allele and genotype comparisons, and odds ratios (OR) with confidence intervals (CI). Mann–Whitney tests assessed correlations between SNP frequencies and disease severity and age onset. A p-value < 0.05 was considered significant. Genotypic variables were analysed using the method described by Liu et al. (15), comparing additive, dominant, recessive, and codominant models.

RESULTS AND DISCUSSION

No significant differences in genotype frequencies were observed between psoriatic patients and controls for the SNPs (Table II) in the population studied. The allele frequency analysis yielded results consistent with the genotype analysis, showing no significant differences in frequencies between healthy individuals and psoriasis patients, nor between patients with mild vs moderate to severe psoriasis and age onset (Table SII). The dominant, recessive, codominant, and additive models were also tested, and no statistical differences were found. However, we observed a trend suggesting that the IL-17RA AG codominant genotype might be more frequent in the moderate to severe group (p = 0.097).

Table II. IL-17RA, TNFα, and TRAF3 genotype and allele frequencies in controls versus psoriasis patients
SNP Genotype allele Controls Psoriasis χ2 p-value OR
rs4819554 (IL17RA) AA 72 (64.9%) 77 (65.8%) 1.07 0.440
AG 36 (32.4%) 34 (29.1%)
GG 3 (2.7%) 6 (5.1%)
A 180 (81.08%) 188 (80.34%) 0.04 0.4216 1.04 (0.65–1.67)
G 42 (18.92%) 46 (19.66%)
rs361525 (TNFα promoter region) GG 110 (90.9%) 103 (85.12%) 2.05 0.086
AG 10 (8.3%) 17 (14.0%)
AA 1 (0.8%) 1 (0.8%)
G 230 (95.04%) 223 (92.15%) 16.89 0.100 0.61 (0.29–1.29)
A 12 (4.96%) 19 (7.85%)
rs33980500 (TRAF3) CC 93 (80.2%) 88 (75.2%) 0.89 0.184
CT 21 (18.1%) 27 (23.1%)
TT 2 (1.7%) 2 (1.7%)
C 207 (89.22%) 203 (86.75%) 0.67 0.208 1.26 (0.72–2.21)
T 25 (10.78%) 31 (13.25%)

Despite previous findings regarding TNF-α alleles in other regions of Brazil, we were unable to replicate these results in our population. This may be attributed to the highly mixed and diverse nature of the Brazilian population, which varies significantly between regions. Another factor to consider is the sample size, and further studies with larger samples are needed to confirm these findings. Additionally, we did not observe the same results for other alleles tested, such as IL17RA in Spain and Act1 (or TRAF3IP2) in Poland. These findings suggest unique genetic architecture in Brazil’s multiracial population, differing from other regions inside the country and across the world. Contrary to prior reports emphasizing TNF-α and HLA-C*06 in Brazilian psoriasis, our results of rs361525, rs4819554, and rs33980500 analysis showed no significant associations. However, trends for IL17RA warrant larger confirmatory studies.

Studies in multiracial populations such as in Brazil are crucial to understanding global genetic variability in psoriasis, informing personalized treatments. Future research should include larger cohorts and longitudinal studies examining genotype–phenotype correlations and treatment outcomes.

ACKNOWLEDGEMENTS

Jeane de Souza Nogueira, Sueli Carneiro, Andrea Monte Alto-Costa, and Luís Cristóvão Porto are deeply acknowledged for their critical review of the final manuscript and their valuable contributions to the discussion.

IRB approval status: Ethics Committee of Hospital Universitário Pedro Ernesto: CAAE 31055720.9.0000.5259.

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