Association of IL-17F rs763780 polymorphism and risk of psoriasis in Turkish population: a case-control study.

BACKGROUND: Psoriasis represents a chronic inflammatory phenotype shaped by genetic interactions, characterized by keratinocyte hyperproliferation and commonly affecting the skin and joints. Experimental and clinical studies suggest that the IL-17F gene locus plays a role as a central cytokine in the immunopathogenesis of psoriasis. OBJECTIVES: Based on the central role of IL-17F in the pathogenesis of psoriasis, the authors thought that variations in this gene could affect the susceptibility and severity of this disease. Therefore, in this study, the authors aimed to analyze whether the IL-17F rs763780 variant has an effect on psoriasis pathogenesis in the Turkish population. METHOD: In this case-control study, the study group consisted of 603 people (201 psoriasis patients (73 males/128 females)/402 controls (146 males/256 females) were genotyped in terms of IL-17F rs763780 polymorphism with TaqMan 5' Allelic Discrimination Test. RESULTS: The genotype distributions of the IL-17F rs763780 polymorphism between patients and control groups were statistically different, and the TC (heterozygous genotype) and CC (homozygous mutant genotype) genotypes were more represented in the patients group than in the control group (24.9% vs. 10.2%; 2.0% vs. 0.2%, respectively). In addition, the variant C allele was higher in the patients group and this was statistically significant (p < 0.001), and the C allele carriage was associated with a 3.14-fold increased risk of psoriasis (95% CI 2.015‒24.921). STUDY LIMITATIONS: The present study has some limitations. The first limitation is the relatively small sample size. The second limitation is that the authors could not measure IL-17F expression levels. However, the present study data draw attention to the importance of IL-17F which deserves to be studied in a larger sample group. CONCLUSION: We report that IL-17F rs763780 TC and CC genotype and C allele are associated with an increased risk of psoriasis in the Turkish population.

Genetic variants in IL-17A rs10484879 and serum levels of IL-17A are associated with psoriasis risk.

Psoriasis is an inflammatory skin disease characterized by keratinocyte hyperproliferation with effective environmental and genetic factors. Recent studies showing that the IL-23/IL-17 axis plays a central role in the pathogenesis of the disease. Experimental and clinical studies suggest that IL-17A, an important regulatory effector cytokine in this pathway and triggers changes mainly in affected tissues. Based on the central role of IL-17A in the pathogenesis of psoriasis, we thought that variations in this gene could affect the susceptibility and severity of this disease. Therefore, in this study, we aimed to analyze whether IL-17A rs10484879 variant has an effect on psoriasis pathogenesis in Turkish population. In this case-control study, the study group consisting of 564 patient (188 psoriasis patients (66 males/122 females)/376 controls (132 males/244 females) and they were genotyped in terms of IL-17A (rs10484879) polymorphism with TaqMan 5 'Allelic Discrimination Test. IL-17A serum levels were measured with the Enzyme-linked immunosorbent assay (ELISA). The genotype distributions of the IL-17A rs10484879 polymorphism between the patient and control groups were statistically different in the TT genotype and it was observed more commonly in the patient group compared to the controls (p < 0.001). Similarly, the T allele was observed with a higher prevalence in the patient group compared to the controls (p = 0.007). IL-17A serum levels were associated with increased serum concentration, respectively, TT > GT > GG in all study groups (p < 0.05). We would like to report that IL-17A rs10484879 TT genotype and T allele are associated with increased risk of psoriasis in the Turkish population.

Hydrogen sulfide dilates the isolated retinal artery mainly via the activation of myosin phosphatase.

AIMS: Hydrogen sulfide (H2S) is shown in ocular tissues and suggested to involve in the regulation of retinal circulation. However, the mechanism of H2S-induced relaxation on retinal artery is not clarified yet. Herein, we aimed to evaluate the role of several calcium (Ca2+) signaling and Ca2+ sensitization mechanisms in the relaxing effect of H2S donor, NaHS, on retinal arteries. MATERIALS AND METHODS: Relaxing effects of NaHS (10-5-3 × 10-3M) were determined on precontracted retinal arteries in Ca2+ free medium as well as in the presence of the inhibitors of Ca2+ signaling and Ca2+ sensitization mechanisms. Additively, Ca2+ sensitivity of the contractile apparatus were evaluated by CaCl2-induced contractions in the presence of NaHS (3 × 10-3M). Functional experiments were furtherly assessed by protein and/or mRNA expressions, as appropriate. KEY FINDINGS: The relaxations to NaHS were preserved in Ca2+ free medium while NaHS pretreatment decreased the responsiveness to CaCl2. The inhibitors of plasmalemmal Ca2+-ATPase, sarcoplasmic-endoplasmic reticulum Ca2+-ATPase, Na+-Ca2+ ion-exchanger and myosin light chain kinase (MLCK) unchanged the relaxations to NaHS. Likewise, Ca2+ sensitization mechanisms including, rho kinase, protein kinase C and tyrosine kinase were unlikely to mediate the relaxation to NaHS in retinal artery. Whereas, a marked reduction was determined in NaHS-induced relaxations in the presence of MLCP inhibitor, calyculin A. Supportively, NaHS pretreatment significantly reduced phosphorylation of MYPT1-subunit of MLCP. SIGNIFICANCE: The relaxing effect of NaHS in retinal artery is likely to be related to the activation of MLCP and partly, to decrement in Ca2+ sensitivity of contractile apparatus.