Significance of interleukin-31 (IL-31) gene polymorphisms and IL-31 serum level in psoriasis in correlation with pruritus (original) (raw)
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Polymorphisms in IL36G gene are associated with plaque psoriasis
BMC Medical Genetics, 2019
Background: Plaque psoriasis is a non-contagious skin disease in which characteristic red and flaky lesions result from a dysregulation involving both innate and adaptive immune mechanisms. Several cytokines have been implicated in these processes and lately interleukin (IL)-36 family members have become more recognised among them. Thus far, genetic studies have only investigated IL36RN gene of this family in relation to pustular psoriasis. Since IL36G has previously demonstrated markedly increased levels in plaque psoriasis patients and is linked to IL-23/IL-17 axis critical in psoriasis pathology, it was chosen to be the focus of current report. Methods: Eleven SNPs from IL36G region were genotyped in 728 plaque psoriasis patients and 320 healthy control individuals. Allele and haplotype frequencies between patients and controls were assessed by respective association tests. For more specific analyses, the patients were assigned into subgroups according to sex, age of disease onset, occurrence of psoriasis among relatives, seasonal aggravation, arthritis symptoms, body surface area (BSA) scores, and Psoriasis Area and Severity Index (PASI) scores. Results: The most significant results were obtained with SNPs rs28947206, rs28947207 and rs28947211 that were associated in entire plaque psoriasis analysis (multiple testing adjusted p value (p adj) = 0.0054, p adj = 0. 0017 and p adj = 0.0001) and also several subgroups. The first two of those SNPs were included in the same haplotype block with rs28947205 and rs12328178, and two of the respective haplotypes, CAGC and TGTT, provided similarly significant associations (p adj = 0.0462 and p adj = 0.0047). Conclusions: The associated SNPs of this study or those in linkage disequilibrium with them could potentially affect the functionality of IL-36γ cytokine, which in turn may impact plaque psoriasis pathology. For instance, these variants could influence IL-36γ expression or 3D structure, thereby altering its ability to induce chemokine production in keratinocytes and various immune cells. The precise mechanisms of these actions are currently unknown and out of the scope of this study. To conclude, the present genetic association results confirm the proposed role of IL-36γ in plaque psoriasis development, with corresponding causal effects to be determined in forthcoming research.
TURKISH JOURNAL OF MEDICAL SCIENCES
Introduction Psoriasis is a chronic inflammatory skin disease characterized by papules and/or plaques that are often covered with silvery-whitish scales [1]. The presence of a family history of psoriasis in about 30% of patients, simultaneous presence of psoriasis in monozygotic twins, and association of early-onset psoriasis with many major tissue antigen alleles, especially human leukocyte antigen (HLA) Cw6, are some of the factors that suggest a role for genetic factors in the occurrence of the disease [2,3]. Although the pathogenesis of psoriasis is not known exactly, dysregulation in T cells is thought to induce keratinocyte proliferation. Studies have shown a prominent role of the helper T-cell (Th) 17/interleukin (IL)-23 pathway in the pathogenesis of psoriasis [4,5]. IL-23 is the key cytokine that directs naive CD 4+ T cells to differentiate into Th17 cells by upregulating the IL-23 receptor (IL-23R) on naive T cells, resulting in the secretion of cytokines [4,5]. Previous studies have shown a significant relationship between psoriasis and some polymorphisms in the IL-23R gene [6,7]. The IL-23R gene consists of 11 exons and 10 introns; it is localized in chromosome 1p31.3 and is 2912 bp long (Figure). The rs2201841, rs11209026, rs11465804, rs7530511, and rs1343152 polymorphisms are located in the 7th intron, 9th exon, 8th intron, 7th exon, and 8th intron, respectively. Our study is the first to investigate the relationship between IL-23R gene polymorphisms and psoriasis in Turkey. Additionally, our study is the first in the literature Background/aim: IL-23R gene polymorphisms and the association of these polymorphisms with serum IL-23 levels were investigated in patients with psoriasis in the current study. Materials and methods: Sixty-seven patients with psoriasis who were admitted to our dermatology outpatient clinic and 67 healthy controls were included in the study. Polymorphisms of the IL-23R gene were determined by KASP-PCR method, and serum IL-23 levels were determined by ELISA method. Results: The distribution of IL-23R gene polymorphisms rs2201841, rs11209026, rs7530511, rs1343152, and rs11465804 was not significantly different in the patient and control groups. The AA genotype of the rs2201841 locus in males and the GA genotype in females, as well as the AA genotype of the rs1343152 locus in males and the CA genotype in females, were statistically significant in patients with psoriasis. The mean serum IL-23 level was significantly lower in the patient group (42.62 ± 5.96) compared to the control groups (75.76 ± 13.24). Conclusion: IL-23R gene polymorphisms including rs2201841, rs11209026, rs7530511, rs11465804, and rs1343152 were not found to be significantly related to psoriasis. Different genetic polymorphisms may play a role in the development of psoriasis in female and male populations. Ethnic differences between different populations may have led to differences in the distribution of polymorphisms in the current study with compared to other published studies. Additionally, many different genes, polymorphisms, and environmental factors that have an effect on the development of psoriasis may affect the disease process.
Study role of interleukin 23 level, family histories and blood groups in psoriasis patients
Annals of Tropical Medicine and Public Health
Background: Psoriasis is the one of important autoimmune diseases with chronic inflammatory signs in skin Erythematous, scaly plaques, and can infect all ages and in all countries. Objectives & Methodology: In order to detect the incidence of Psoriasis and its association with elevated IL-23, 70 people were involved in the current study, their ages were (1-45) years and from both genders 30 of them was with Psoriasis and the family history groups 20 and the other healthy 20 were cosidered as control groups. This study was worked in the central health laboratory, Hilla Teaching Hospital in the peroid Nov.2018 to Feb.2019 in Babylon Governorate. Results: the IL-23 of in Psoriasis patients has a significant with same results in family history groups in all age groups when comparison with control group. The results also showed that patients of blood group (O+) are the most frequent by percent (33.33) followed by B+, A+ , AB+ and AB¯ with percent reached (30%,20%,10% and 6. 67%) respectively. Furthermore, there is a genetic tendency in the frequency of onset of Psoriasis as 20% in both parents and (30&10 %) in mothers and fathers respectively while 40% of the disease does not appear in their families. Results also showed significant increasing in the age groups (31-45) years in comparison with (1-15) and (16-30) years. The disease also rises in males compared with females. Conclusions: a significant increase in IL-23for patients with Psoriasis compared with the control group. Patients with family history are at high risk to develop Psoriasis. The age group (31-45) found to have high incidence of Psoriasis compared with other age groups. Persons of O+ blood groups may be at high risk to have Psoriasis.
—Genome-wide association studies of psoriasis identified interleukin (IL)-12B and IL-23R as significantly associated loci with psoriasis, thus emphasizing to the important role of these genes in the pathogenesis of this disease and have influenced the development of medications that specifically target these key immunological players. Here we report an association study of a homogeneous Greek cohort from the island of Crete, consisting of 100 patients with PS and 195 controls, which were genotyped for rs3212227 and rs6887695 SNPs of the IL-12B and the rs7530511 and rs11209026 SNPs of IL-23R genes, respectively, using Taqman assays. Neither IL12B nor IL23R SNPs showed any association with psoriasis in the population under study. Apart from the previously reported evidence for the role of IL-12B and IL-23R in various populations, our results demonstrate no association of these gene polymorphisms with psoriasis in the Cretan population, thus highlighting the importance of comparative studies in different populations to confirm the previously detected genetic associations.
Candidate gene polymorphisms and risk of psoriasis: A pilot study
Experimental and Therapeutic Medicine, 2016
Psoriasis is a complex genetic disease, which has previously been associated with numerous single nucleotide polymorphisms (SNPs) that are implicated in various processes, including skin barrier functions and in the regulation of inflammatory and immune responses. The present study aimed to investigate the genotypic and allelic frequencies of 32 SNPs at 24 genetic loci, and their association with psoriasis in a Mexican population. These SNPs, which were associated with psoriasis in previous studies, included the following genes: Major histocompatibility complex class I-C (HLA-C), interleukin (IL)-12B, IL-23R, IL-23A, IL-28RA, tumor necrosis factor (TNF)-α, ring finger protein-114 (RNF114), cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1, late cornified envelope 3B/3C, signal transducer and activator of transcription 4, LINC01185, interferon induced with helicase C domain 1, IL-13, TNF-α-induced protein 3 (TNFAIP3), TNFAIP3 interacting protein 1, endoplasmic reticulum aminopeptidase 1, TNF receptor-associated factor interacting protein 2, Leptin, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha, F-box and leucine-rich repeat protein 19, nitric oxide synthase 2, cluster of differentiation 40, nuclear receptor coactivator 5, and ADAM metallopeptidase domain 33. A total of 32 male and 14 female subjects with a clinical diagnosis of chronic plaque psoriasis, as well as 103 control subjects, were analyzed. Molecular analyses were performed using TaqMan ® assays in a TaqMan ® OpenArray ® Genotyping system. Results were analyzed using the Golden Helix SNP and Variation Suite 7 program. Of the 32 SNPs, six were associated with an increased risk of developing psoriasis, including: HLA-C rs10484554 [allele T: odds ratio (OR) 3.51], IL-12B rs3212227 (allele T: OR 1.88), IL-12B rs3213094 (allele C: OR 1.94), HLA complex group 27 rs1265181 (allele C: OR 2.83), annexin A6 rs17728338 (allele A: OR 2.41), and RNF114 rs6125829 (allele G: OR 1.98). Fisher's exact test detected statistical significance; however, following false discovery rate and Bonferroni correction, this association was no longer significant (threshold for genome-wide significance, P<1.56x10-3). SNPs that were associated with an increased risk of psoriasis in the present study have previously been associated with psoriasis in European, American, and Asian populations. In order to establish genome-wide significance, future studies must analyze a greater sample size. To the best of our knowledge, the present pilot study is the first to investigate the association between these 32 SNPs and psoriasis in a Mexican Mestizo population.