title: Evaluation of blood redox-balance, nitric oxide content and CCR6 rs3093024 in the genetic susceptibility during psoriasis.
abstract: The aim of our study was to evaluate whether this polymorphism of CCR6 gene and oxidative stress are associated with psoriasis risk in Caucasian population. The association of the CCR6 polymorphism in the genetic susceptibility of psoriasis was performed at the Department of Dermatology and Venereology, Policlinico Umberto I of Rome (Italy). 516 participants were enrolled including 127 patients affected with psoriasis and 389 healthy controls. Cases and controls were genotyped, using a commercially available assay (Life Technologies, Carlsbad, California, USA) for CCR6 rs3093024 polymorphism. To verify the relations between genotypes and psoriasis risk we evaluated genotype frequencies for each individual DNA polymorphism in both case and control series. There were no differences in the genotype frequencies of the polymorphism between psoriasis cases and healthy controls. When patients with arthropathic psoriasis were excluded from the analysis, logistic regression showed that allele A was likely to reduce the risk of developing psoriasis in a dominant model. Logistic regression showed that male patients harboring the heterozygous genotype GA presented a reduced risk of developing psoriasis, compared with the reference GG genotype. None of the clinical features as age at onset, gender, family history of psoriasis, type of psoriasis, severity, BMI, smoking history or alcohol consumption, were associated with the genotype frequencies of the tested CCR6 polymorphism. In blood samples of patients with psoriasis intensive EPR signals of lipoperoxide (LOO.) free radicals were detected. Activity of blood SOD was significantly decreased in psoriatic patients compared to healthy controls. Activity of catalase was significantly increased in psoriatic patients, reflecting a high concentration of peroxide radicals. In blood samples of psoriatic patients decrease of free spin-trapped NO content were detected, that may be explained by biological transformation of NO into other reactive nitrogen species (proxy nitrite or nitrosylated hemoglobin). Thus, the alterations of redox-balance and NO degradation leads to development of skin perfusion impairments, disorder of proliferation and transcription of cell cycle, initiation of T-cell mediated immune responses, formation of chemokine receptor 6 (CCR6) related with intensification of cellular infiltration in the psoriatic plaques. Furthermore, correction of redox-balance is responsible for inhibiting CCR6 formation resulted in suppressed cellular infiltration with concomitant decrease in oxidative stress. The data reviewed suggest the necessity of evaluation of other blood redox-balance and nitric oxide in psoriasis should with additional investigations to targeting CCR6 rs3093024 in the genetic susceptibility of psoriasis.
authors: Tbilisi State Medical University, Department of Dermatology and Venereology, Department of Medical Physics and Biophysics, Department of Human Normal Anatomy, Georgia; University of Rome "Sapienza", Department of Dermatology and Venereology, Italy.
authors: M
authors: M
authors: Matoshvili
authors: Tbilisi State Medical University, Department of Dermatology and Venereology, Department of Medical Physics and Biophysics, Department of Human Normal Anatomy, Georgia; University of Rome "Sapienza", Department of Dermatology and Venereology, Italy.
authors: A
authors: A
authors: Katsitadze
authors: Tbilisi State Medical University, Department of Dermatology and Venereology, Department of Medical Physics and Biophysics, Department of Human Normal Anatomy, Georgia; University of Rome "Sapienza", Department of Dermatology and Venereology, Italy.
authors: T
authors: T
authors: Sanikidze
authors: Tbilisi State Medical University, Department of Dermatology and Venereology, Department of Medical Physics and Biophysics, Department of Human Normal Anatomy, Georgia; University of Rome "Sapienza", Department of Dermatology and Venereology, Italy.
authors: D
authors: D
authors: Tophuria
authors: Tbilisi State Medical University, Department of Dermatology and Venereology, Department of Medical Physics and Biophysics, Department of Human Normal Anatomy, Georgia; University of Rome "Sapienza", Department of Dermatology and Venereology, Italy.
authors: S
authors: S
authors: D'Epiro
authors: Tbilisi State Medical University, Department of Dermatology and Venereology, Department of Medical Physics and Biophysics, Department of Human Normal Anatomy, Georgia; University of Rome "Sapienza", Department of Dermatology and Venereology, Italy.
authors: A
authors: A
authors: Richetta
mesh_terms: D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000097:blood* / Q000235:genetics; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011565:Psoriasis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D054399:Receptors, CCR6 / Q000097:blood / Q000235:genetics*
chemical_list: C106311:CCR6 protein, human; D054399:Receptors, CCR6; D009569:Nitric Oxide