ABSTRACT
The role of interleukin-23 is crucial in the pathogenesis of psoriasis, and IL23A, IL12B and IL23R genetic variants have been associated with the disease in genome-wide association studies. In the current paper we have conducted a confirmation study of the abovementioned genetic factors in a case-control analysis of 507 psoriatic patients and 396 controls from a Polish population, and subsequently analyzed the impact of genetic variants on response to topical and NB-UVB therapy in a subset of 306 patients. Case-control analysis revealed an association of IL12B rs3212227 and IL23R rs11209026 minor allele carrier status with reduced odds for psoriasis (ORâ¯=â¯0.66, 95%CI: 0.50-0.87, and ORâ¯=â¯0.41, 95%CI: 0.26-0.67, respectively), while HLA-C*06 allele carriers were more frequent in patients group (ORâ¯=â¯4.56, 95%CI: 3.41-6.10). The studied polymorphic variants of IL12B, IL23A, and IL23R genes did not influence therapy outcome, i.e. there were no significant differences in PASI reduction between patients with different genotypes. However, HLA-C*06 carriers showed poorer response to the applied treatment, when compared to non-carriers. The results of the current study confirm an association between IL12B and IL23R genetic polymorphism and psoriasis vulgaris (with a protective effect of minor alleles). HLA-C*06 carriers show reduced effectiveness of topical/NB-UVB therapy, and that observation could be potentially used in treatment personalization.
Subject(s)
HLA-C Antigens/genetics , Interleukin-12 Subunit p40/genetics , Interleukin-23 Subunit p19/genetics , Psoriasis/genetics , Receptors, Interleukin/genetics , Adult , Alleles , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Haplotypes , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Psoriasis/therapy , Treatment Outcome , Ultraviolet Therapy/methodsABSTRACT
BACKGROUND: Recent studies have revealed the pivotal role of Th17 cells and interleukin-17 (IL-17) in plaque psoriasis development and treatment outcome. The IL-17 family consists of 6 structurally related cytokines (IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F), of which IL-17A and IL-17F mediate similar biological effects. OBJECTIVES: The aim of this study was to evaluate an association between the IL17A (-197G>A; rs2275913) and IL17F (rs763780: T>C; rs11465553: G>A; rs2397084: T>C) polymorphisms with psoriasis susceptibility as well as response to topical and combined topical with narrow-band ultraviolet B (NB-UVB) therapy in a Polish population. METHODS: Association study involving 407 psoriasis patients and 205 healthy controls. Treatment efficacy was analyzed in 207 patients with mild psoriasis (Psoriasis Area and Severity Index; PASI 3-12) and moderate psoriasis (PASI 12-18), who were randomly subjected to topical or combined topical and NB-UVB treatment. The polymorphisms were evaluated by RT-PCR. RESULTS: No statistically significant differences between psoriasis patients and controls were found in the frequency of the evaluated IL17A and IL17F genotypes and haplotypes. The IL17A or IL17F polymorphisms were not associated with treatment outcome measures: efficacy of treatment at the eighth week of the study and PASI change after topical or combined topical and NB-UVB therapy. However, IL17F rs2397084 variant allele C carriers required a significantly higher number of NB-UVB irradiations in comparison to TT homozygotes (15.5 ± 11.4 vs. 11.1 ± 11.9, p = 0.047) to produce a positive clinical response. CONCLUSION: It can be stated that the IL17A and IL17F polymorphisms are not markers of susceptibility to psoriasis. However, the IL17F polymorphism may affect the response to NB-UVB therapy.
Subject(s)
Dermatologic Agents/therapeutic use , Interleukin-17/genetics , Psoriasis/genetics , Psoriasis/therapy , Ultraviolet Therapy , Administration, Cutaneous , Adult , Case-Control Studies , Combined Modality Therapy , Dermatologic Agents/administration & dosage , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Poland , Polymorphism, Single Nucleotide , Random Allocation , Risk Factors , Severity of Illness IndexABSTRACT
Interleukin-6 (IL-6) is implicated in the pathogenesis of psoriasis as well as in its treatment efficacy. The aim of this study of 406 patients with psoriasis and 203 healthy controls was to evaluate the association between the IL6 -174G>C (rs1800795) polymorphism and psoriasis susceptibility, as well as treatment efficacy. The frequency of genotype GG (33.7% vs. 20.7%; P = 0.00022; OR = 0.51, 95% confidence interval 0.34-0.76) and of allele G (56.2% vs. 46.8%; P = 0.0023) was significantly higher in the psoriasis group compared with controls. No polymorphism variants were associated with better response to topical or combined topical/narrow-band ultraviolet B (NB-UVB) treatment. We conclude that the IL6 -174G>C polymorphism can be a marker of susceptibility to psoriasis, with an almost twofold increased risk of the disease in individuals carrying the GG genotype; however, it was not associated with treatment response to topical and/or NB-UVB therapy.
