Renata N Cardili1, Neifi S Deghaide2, Celso T Mendes-Junior3, Eduardo A Donadi2, Cacilda S Souza1. 1. Division of Dermatology, Internal Medicine Department, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. 2. Division of Immunology, Internal Medicine Department, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. 3. Chemistry Department, School of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Abstract
BACKGROUND: Polymorphisms at the human leukocyte antigens (HLA-C) and tumor necrosis factor (TNF) genes have been associated with susceptibility to psoriasis in several worldwide populations. In this study, HLA-C and TNF (-238/-308) polymorphisms were performed in 125 Brazilian patients and 202 healthy controls. METHODS: HLA-C and TNF promoter region alleles were typed by polymerase chain reaction using sequence-specific primer-polymerase chain reaction. RESULTS: The presence of HLA-C*06 was associated with psoriasis onset, particularly in younger patients, being more frequent for patients with disease onset before the age of 20 years (P = 0.03), 25 years (P = 0.01), or 30 years (P = 0.03). No association between HLA-C*06 and psoriasis was observed for patients older than 35 years. Susceptibility to psoriatic arthritis was associated with the TNF -238 G/A genotype (P = 0.02). The TNF -308A allele was overrepresented in patients (P = 0.0061), and the TNF -308 G/A genotype was increased in generalized forms (erythrodermic and generalized pustular psoriasis) compared to plaque psoriasis (P < 0.001). The TNF -238A/HLA-C*06 haplotype was overrepresented in patients (P = 0.025), while the TNF -238G/HLA-C*15 haplotype was increased in controls (P = 0.037). CONCLUSIONS: The strong association of HLA-C*06 allele with disease susceptibility, particularly in early onset psoriasis, indicates that younger ages could be considered to stratify psoriasis into early and late types. TNF -308 polymorphisms can be associated with psoriasis susceptibility and severity. Potential genetic markers of psoriasis in populations with a complex mixture of ethnicities should be investigated.
BACKGROUND: Polymorphisms at the human leukocyte antigens (HLA-C) and tumor necrosis factor (TNF) genes have been associated with susceptibility to psoriasis in several worldwide populations. In this study, HLA-C and TNF (-238/-308) polymorphisms were performed in 125 Brazilian patients and 202 healthy controls. METHODS:HLA-C and TNF promoter region alleles were typed by polymerase chain reaction using sequence-specific primer-polymerase chain reaction. RESULTS: The presence of HLA-C*06 was associated with psoriasis onset, particularly in younger patients, being more frequent for patients with disease onset before the age of 20 years (P = 0.03), 25 years (P = 0.01), or 30 years (P = 0.03). No association between HLA-C*06 and psoriasis was observed for patients older than 35 years. Susceptibility to psoriatic arthritis was associated with the TNF-238 G/A genotype (P = 0.02). The TNF -308A allele was overrepresented in patients (P = 0.0061), and the TNF-308 G/A genotype was increased in generalized forms (erythrodermic and generalized pustular psoriasis) compared to plaque psoriasis (P < 0.001). The TNF -238A/HLA-C*06 haplotype was overrepresented in patients (P = 0.025), while the TNF -238G/HLA-C*15 haplotype was increased in controls (P = 0.037). CONCLUSIONS: The strong association of HLA-C*06 allele with disease susceptibility, particularly in early onset psoriasis, indicates that younger ages could be considered to stratify psoriasis into early and late types. TNF -308 polymorphisms can be associated with psoriasis susceptibility and severity. Potential genetic markers of psoriasis in populations with a complex mixture of ethnicities should be investigated.