Evaluation of interleukin-23 receptor (IL-23R) gene polymorphisms and serum IL-23 levels in patients with psoriasis

Abstract

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 ge...

Assessing the Short-Term Efficacy and Safety of Guselkumab for Moderate-to-Severe Plaque Psoriasis: Meta-Analysis of Randomized Controlled Trials

“…IL-23 belongs to the IL-12 cytokine family. It is a heterodimer composed of p40 and p19 subunits [ 8 ]. Guselkumab is a fully human immunoglobulin G 1 λ (IgG 1 λ ) monoclonal antibody that blocks the downstream signaling of IL-23 by specifically binding to the p19 subunit of IL-23 [ 9 ].…”

Search for genetic markers of predisposition to psoriasis and psoriatic arthritis

“…Есть данные о повышении концентрации данных провоспалительных цитокинов как в очагах псориатического поражения кожи, так и в суставной жидкости больных псориатическим артритом [12,15] [14]. IL-23 принадлежит к небольшой группе гетеродимерных цитокинов, имеющих общую субъединицу p40 [7]. Терапия моноклональными антителами, содержащими субъединицы р40 и р19, продемонстрировала высокую клиническую эффективность у больных псориазом [14].…”

“…Есть сведения, что концентрация IL-23 статистически значимо выше в сыворотке и очагах поражения кожи больных ПС в сравнении с контролем [4]. В других исследованиях было продемонстрировано, что концентрация IL-23 в сыворотке крови больных ПС была значительно ниже в сравнении с контрольной группой [7]. В геномных исследованиях выявлено несколько генов, кодирующих обе субъединицы цитокина IL-23 (IL12Bp40 и IL23Ap19), а также рецептор IL-23 (IL23R), ассоциированных с псориазом [5].…”

“…Данные с обратной комплементарной цепи ДНК (-) показывают, что альтернативные генотипы CT и CC в локусе rs2201841 (T>C) статистически значимо встречаются чаще в группе больных ПС в сравнении с контролем, однако генотип CC был ассоциирован с высокой концентрацией IL-23 в сыворотке крови [8]. Определено, что генотип АА локуса rs2201841 (A>G) у мужчин и генотип GА у женщин встречались статистически значимо чаще у больных ПС [7]. В других исследованиях, напротив, не было обнаружено существенных различий в носительстве генотипов AA, GA и GG в локусе rs2201841 у больных ПС и в контрольной группе [5,7].…”

“…Определено, что генотип АА локуса rs2201841 (A>G) у мужчин и генотип GА у женщин встречались статистически значимо чаще у больных ПС [7]. В других исследованиях, напротив, не было обнаружено существенных различий в носительстве генотипов AA, GA и GG в локусе rs2201841 у больных ПС и в контрольной группе [5,7].…”