Interleukin-23 Receptor Gene Polymorphisms Research Articles

Gene polymorphisms of an interleukin-23 receptor associated with susceptibility to rheumatoid arthritis in the Western Chinese Han population.

Rheumatoid arthritis (RA) is a chronic inflammatory disease which is closely related to genetic background. Single-nucleotide polymorphisms (SNPs) have been found to play an important role in the development of RA. This study intends to investigate the links between gene polymorphisms in the interleukin-23 receptor (IL23R) and interleukin 17A (IL17A) and susceptibility to RA in the Western Chinese Han population. Four SNPs (rs6693831 T>C, rs1884444 G>T, and rs7517847 T>G in IL23R gene, and rs2275913 G>A in IL17A gene) were genotyped in 246 RA patients and 362 healthy controls by high resolution melting analysis. The comparative analyses among genotype distributions, clinical indicators, and IL-17A and IL-23R levels in RA patients were also performed. The study revealed that the SNP rs6693831 and rs1884444 of IL23R had a significant association with RA susceptibility. The frequencies of rs6693831 genotype CC and allele C were significantly higher in the RA group and associated with higher RA risk compared with genotype TT and allele T (OR=7.797, 95% confidence interval [CI]=4.072-14.932 and OR=5.984, 95%CI=3.190-11.224, respectively). The TT genotype of rs1884444 appeared to decrease the RA risk compared with the GG genotype (OR=.251, 95%CI=.118-.536). The genotype CC and allele C of rs6693831 and the genotype GG and allele G of rs1884444 may be risk factors for RA. IL23R gene polymorphisms may be involved in the risk of RA susceptibility in the Western Chinese Han population.

Interleukin-23 receptor gene polymorphisms in osteoporosis

Objectives: Osteoporosis (OP) is a usual disease with a possible genetic predisposition. IL-23 plays a role in physiological bone remodeling and regulates the activity of cells of the bone either directly or indirectly on bone-resorbing osteoclasts as well as on bone-forming osteoblasts. Recent animal and human trials have revealed the main pro-osteoclastogenic activities for the IL-23 pathway. We examined nine single nucleotide polymorphisms (SNPs) in the interleukin-23 receptor (IL-23R) in 100 OP patients and gender- and age-matched 96 healthy volunteers. The most analyzed SNPs in the recent rheumatology literature were selected. Methods: In addition to gene polymorphisms several laboratory parameters (osteocalcin, parathormone, vitamine D) were investigated. Independent Samples t-test and Mann-Whitney-U test were used to compare several demographic and clinical parameters between the groups. P-value < 0.05 was accepted to be statistically significant. Results: Having the heterozygous GA genotype of IL-23R rs1004819 and the heterozygous CT genotype of Il-23R rs7530511 significantly increase the risk of developing OP (adjusted OR: 3.51, p = 0.031 and OR: 2.41, p = 0.027, respectively). The wild homozygous GG genotype of Il-23R rs11209032 had higher osteocalcin levels compared with the mutant homozygous AA genotype (18.75 ± 9.76, p = 0.009). Conclusions: Our findings suggest that several IL-23R gene polymorphisms are seen more often in osteoporosis patients than in healthy volunteers. In addition, some SNPs were related to higher serum osteocalcin levels.

IL-23R gene polymorphisms in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease in which many different genetic variants of functional gene polymorphisms may play a culprit role in the underlying pathogenetic mechanism. The recent studies suggest that interleukin-23 receptor (IL-23R) gene polymorphisms may increase susceptibility to the development of various autoimmune diseases. We aimed to examine the possible relationship of nine single nucleotide polymorphisms (SNPs) in the IL-23R gene to susceptibility to rheumatoid arthritis and their associations with disease characteristics in the South Aegean region of Turkey. We enrolled 100 rheumatoid arthritis patients and age- and sex-matched 96 healthy subjects in the study. After deoxyribonucleic acid (DNA) isolation was performed, a 'Restriction Fragment Length Polymorphism' (RFLP) method was used for the investigation of polymorphisms associated with the IL-23R gene. Allele identification and genotyping were obtained from polymerase chain reaction (PCR) products using gel electrophoresis. Allele frequencies and detected genotypes were compared between groups. All statistical analyses were performed using SPSS 25.0 (IBM SPSS Statistics 25 software (Armonk, NY: IBM Corp.)). Continuous variables were defined by the mean ± standard deviation and categorical variables were defined by number and percent. Logistic Regression Analysis was used for determining which variables affect the presence of RA. Differences between categorical variables were analyzed with Chi-square analysis. Statistical significance was determined as p < 0.05. The mean age was 53.48 ± 11.7years in the RA group, whereas 52.55 ± 12.7years in the healthy control group. The genotypes of IL-23R with rs11805303(TT), rs10889677(AA), rs1004819(AA), and rs7530511(CT) polymorphisms were seen more often in RA patients than healthy controls. Having the AA genotype of IL-23R rs1004819 and the CT genotype of Il-23R rs7530511 increase the development risk of RA with a statistical significance (OR: 3.416 p = 0.003 and OR: 4.899 p = 0.0001, respectively). RA patients with the CC genotype of Il-23R with rs11805303, the CC genotype with rs10889677, and the TT genotype with rs2201841 of the IL-23R gene had higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels than with other genotypes. RA patients with the CC genotype rs11805303 and the GG genotype rs1004819 of the IL-23R gene had more active disease. Our findings suggest that all of the nine analyzed IL-23R gene polymorphisms are seen more frequently than healthy controls in our study population. Besides, some SNPs were related to higher acute phase reactants and higher disease activity scores.

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

Background/aimIL-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 methodsSixty-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.ResultsThe 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.

Interleukin-23 receptor gene polymorphisms in Iranian patients with juvenile systemic lupus erythematosus

Introduction and objectivesConsidering the possible roles of interleukin-23 receptor (IL-23R) gene in the pathogenesis of juvenile systemic lupus erythematosus (JSLE), the objective of this study was to elucidate whether polymorphisms of the IL23R are associated with susceptibility to JSLE in an Iranian population. Materials and methodsA case-control study on 62 patients with JSLE and 78 healthy controls was performed to investigate the associations of four single nucleotide polymorphisms (SNPs) in IL-23R gene, namely, rs7517847, rs10489629, rs11209026, and rs1343151, with susceptibility to JSLE, using real-time polymerase chain reaction Taqman genotyping technique. ResultsAnalysis of allele and genotype frequency of four selected SNPs revealed statistically significant positive association between homozygous variant of rs7517847 (TT) (P, 0.02) and T allele at the same position (P, 0.01) with JSLE vulnerability. There was no significant association between other evaluated SNPs and JSLE susceptibility. ConclusionThese findings suggest that particular IL-23R gene variants could affect individual susceptibility to JSLE.

Relationship between IL-23R gene polymorphism and susceptibility to acute coronary syndrome

Objective To investigate the relationship between the rs6682925T/C gene polymorphism of interleukin (IL)-23 receptor (IL-23R) gene and susceptibility to acute coronary syndrome (ACS). Methods A case-control study. 180 ACS patients (the disease group) and 90 patients with normal coronary angiography(control group) were selected from January 2017 to April 2018 in jingzhou central hospital. The disease group included 109 males and 71 females,aged (59.95±9.29) years old and the control group included 49 males and 41 females, aged (58.39±9.43) years old. The gene polymorphism of IL-23R gene rs6682925T/C was detected by Sanger sequencing,and serum IL-23R concentration in peripheral blood was detected by ELISA. The statistical analysis methods used include normal distribution test,t test,analysis of variance and chi-square (χ2) test. Unconditional logistic regression analysis of the relationship between IL-23R gene rs6682925T/C polymorphism and susceptibility to ACS. Results There were no significant differences in gender, age, body mass index, apolipoprotein b, total cholesterol and low-density lipoprotein cholesterol between the ACS group and the control group(χ2=0.923, P>0.05; t=1.294, P>0.05; t=-0.574, P>0.05; t=-0.417, P>0.05). However, the differences in triglyceride, fasting blood glucose, high-density lipoprotein cholesterol,smoking rate,diabetes and hypertension were statistically significant(t=5.411, P<0.05; t=5.828, P<0.05; t=-6.655, P<0.05; χ2=7.738, P<0.05; χ2=13.201, P<0.05; χ2=8.359, P<0.05). Compared with the control group, the IL-23R rs6682925 polymorphic site in ACS group had significant differences in the distribution of TT, CT, CC genotype and C allele frequency (χ2=9.858, P<0.05; χ2=10.833, P<0.05) and the frequency of C allele in the acute coronary syndrome group was significantly higher than that of the control group. In addition, the risk of rs6682925 CC genotype carriers suffer from acute coronary syndrome was 3.261 times that of TT genotype (95% CI:1.553-6.847,P=0.002). Compared with the control group,the serum IL-23R concentration in the peripheral blood of the ACS group was significantly increased [(353.20±140.79) pg/ml vs (187.41±123.36) pg/ml,t=9.495,P<0.01]. Conclusions IL-23R rs6682925 gene polymorphism is associated with genetic susceptibility to ACS,and the rs6682925 CC genotype might act as a risk factor for ACS. Key words: Interleukin-23 receptor; Single nucleotide polymorphism; Acute coronary syndrome; Disease susceptibility

Interleukin-23 receptor (IL-23R) gene polymorphisms and haplotypes associated with the risk of preeclampsia: evidence from cross-sectional and in silico studies.

Pre-eclampsia is a relatively common pregnancy disorder. Serum concentrations of certain pro-inflammatory molecules and cytokines like interleukin-23 may affect the pathogenesis of pre-eclampsia. The interleukin-23 receptor (IL-23R) gene plays an important role in the progression of inflammatory and autoimmune diseases and IL-23 polymorphisms might influence the susceptibility of pre-eclampsia. The aim of the recent study was to establish the association between IL-23R gene polymorphisms and the susceptibility for developing of pre-eclampsia. One hundred and fifty-eight pregnant patients with pre-eclampsia and 153 controls were genotyped using RFLP-PCR and AS-PCR. Also, an in silico analysis was performed to predict possible effects of these variations on IL-23R mRNA and protein structures. The frequency of the AG genotype of rs11209026 is related to a higher risk of pre-eclampsia. The mutant C and A allele in rs10889677 and rs11209026 SNPs, respectively, are correlated with the risk of pre-eclampsia and they are more frequent in severe late onset PE. We found higher frequency of the haplotype CG in patients with pre-eclampsia in comparison to healthy controls, as well as, the CG haplotype frequency significantly increased the risk of PE in severe, early onset, and late onset sub-groups. The results of computational analysis predicted rs11209026 and rs10889677 SNPs as functional variations, which can influence IL-23R mRNA and protein. The results of present study show positive association between polymorphisms in the IL-23R gene and pre-eclampsia. Therefore, the presence of IL-23R rs11209026, rs10889677 polymorphism might be markers for the genetic susceptibility to pre-eclampsia.

Are genetic variations in IL-21-IL-23R-IL-17A cytokine axis involved in a pathogenic pathway of rheumatoid arthritis? Bayesian hierarchical meta-analysis.

Inflammatory cytokines have been established to be involved in the pathogenesis of rheumatoid arthritis (RA). The genetic polymorphisms in the interleukin (IL) 23 receptor (IL23R), IL21, and IL17 have been associated with RA risk. However, there is no conclusive understanding of the genes encoding the immunoinflammatory IL-21-IL-23R-IL-17A pathway in RA aetiopathogenesis. This meta-analysis was conducted to attain this goal. A comprehensive literature search was conducted in Scopus and PubMed to look for the relevant case-control studies up until 2018. A Bayesian hierarchical meta-analysis was carried out to assess the association between the polymorphisms and the risk of RA. The association was estimated by calculating the logarithm of odds ratio (Log OR) and 95% credible interval (95% CI). In this meta-analysis, 37 case-control studies comprising 23,506 RA patients and 25,984 healthy individuals were found for analyzing the IL23R, IL21, and IL1A gene polymorphism and risk of RA. In the IL23R gene rs1343151 SNP, the minor A allele significantly increased the risk of RA (Log OR = 0.085, 95% CI = 0.008, 0.156). Moreover, the minor AA genotype was significantly associated with increased RA risk (Log OR = 0.176, 95% CI = 0.028, 0.321). In addition, the C allele of the IL23R gene rs2201841 SNP significantly decreased the disease risk (Log OR = -0.544, 95% CI = -1.0, -0.065). Since Bayesian meta-analysis is a powerful strategy to pool the data, it can be mentioned that genetic polymorphisms of IL23R, but not IL21 and IL17A, are involved in susceptibility to RA.

Associations between IL-23R gene polymorphisms and the susceptibility of rheumatoid arthritis: a meta-analysis

Objective: This meta-analysis was aimed to verify the influences of interleukin 23 receptor (IL-23R) rs11209026 and rs2201841 polymorphisms on the susceptibility of rheumatoid arthritis (RA).Methods: We searched potentially relevant studies on the relationships of IL-23R gene rs11209026 and rs2201841 polymorphisms with RA susceptibility from PubMed (Medline), CNKI and EMBASE web databases. Crude odds ratios (ORs) along with 95% confidence intervals (95% CIs) were calculated to assess the strength of association through the fixed- or random-effects model.Results: Eight published articles containing 5544 RA patients and 5532 health individuals were included in our meta-analysis. In total analysis, we found IL-23R gene rs11209026 polymorphism was not related to RA susceptibility in all genetic models, but there was a significant association between rs2201841 polymorphism and RA susceptibility under G vs. A model. In stratified analysis by ethnicity, an increased RA susceptibility was detected for rs2201841 polymorphism in Caucasian group.Conclusion: The results of meta-analysis indicated that IL-23R gene rs2201841 polymorphism might be a susceptible factor for RA under G vs. A model, especially in Caucasian population.

Complex role of IL-23R polymorphisms on ankylosing spondylitis: a meta-analysis

ABSTRACTBackground: The aim of the meta-analysis was to evaluate the association between 10 widely studied polymorphisms of interleukin-23 receptor gene (IL-23R) and ankylosing spondylitis (AS).Methods: A comprehensive literature search, screening of eligible articles and data extraction was performed independently by two investigators. Further meta-analysis was conducted with STATA 12.0 software (Stata Corp.; College Station, TX, USA). The association between IL-23R polymorphisms and AS was evaluated by odds ratio (OR) and 95% confidence intervals (95% CI).Results: Twenty-five case–control studies with 8431 cases and 8972 controls were included in this meta-analysis. Quantitative meta-analysis revealed that minor allele frequency (MAF) of rs1004819, rs1495965, and rs2201841 was significantly higher in the AS group (p value < .001, < .001, = .010, respectively). MAF of rs10489629, rs11209026, rs11465804, and rs1343151was significantly lower in the AS group (p value = .002, < .001, = .032, < .001, respectively). However, there is no significant difference between these two groups in rs10889677, rs11209032, and rs7517847 frequency (p value = .128, .237, .131, respectively).Conclusions: The present study indicates that minor allele carriers of rs1004819, rs1495965, and rs2201841 are susceptible to AS. Conversely, minor alleles of rs10489629, rs11209026, rs11465804, and rs1343151 have protective effect on AS.

Interleukin-23R gene polymorphism in pediatric Egyptian patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia is an acquired autoimmune disorder caused by the production of antiplatelet antibodies. These autoantibodies opsonize platelets for splenic clearance, resulting in low levels of circulating platelets. The current case-control study aimed at detecting the frequency of interleukin-23 receptor rs1884444 single nucleotide polymorphism in Egyptian children with primary immune thrombocytopenia and its possible role as a genetic marker for disease risk. Interleukin-23 receptor rs1884444 single nucleotide polymorphism was studied in 50 patients with primary immune thrombocytopenia and 100 healthy age and sex-matched controls by polymerase chain reaction amplification of the target gene followed by allele-specific restriction enzyme digestion. Regarding the distribution of the genotypes of the interleukin-23 receptor rs1884444 polymorphism, no statistically significant difference was found between cases and control groups. The variant genotypes (GT/TT) frequency was 10% in primary immune thrombocytopenia cases versus 7% in the control groups [P value = 0.755, odds ratio (OR): 0.326, 95% confidence interval (CI): 0.099-1.076]. Similarly, no difference was found between acute and chronic cases. The variant genotypes GT/TT frequency was 10.7% in acute versus 9.1% in chronic primary immune thrombocytopenia (P value = 0.849). The variant genotypes GT/TT were not found to be a risk factor for acute primary (P value = 0.807, OR: 0.641, 95% CI: 0.16-2.563) or chronic primary immune thrombocytopenia (P value = 0.914, OR: 0.762, 95% CI: 0.153-3.797). Our study suggests the possibility that interleukin-23 receptor gene polymorphism may not contribute to the susceptibility of development of primary immune thrombocytopenia in Egyptian children.

Association of Interleukin-23 receptor gene polymorphisms with susceptibility to Crohn’s disease: A meta-analysis

Studies investigating the association between Interleukin-23 receptor (IL-23R) gene polymorphisms and Crohn’s disease (CD) report conflicting results. Thus, a meta-analysis was carried out to assess the association between the IL-23R polymorphisms and CD. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CIs) was used to estimate the strength of association. Finally, a total of 60 case-control studies in 56 articles, involving 22,820 CD patients and 27,401 healthy controls, were included in the meta-analysis. Overall, a significant association was found between all CD and the rs7517847 polymorphism (OR = 0.699, 95% CI = 0.659 ~ 0.741, P < 0.001). Meta-analysis of the rs11209026, rs1343151, rs10489629 and rs11465804 polymorphisms indicated the same pattern as for rs7517847. Meta-analysis showed an association between the rs10889677A allele and CD (OR = 1.393, 95% CI = 1.328 ~ 1.461, P < 0.001). Similarly, meta-analysis of the rs2201840, rs1004819, rs1495965 and rs11209032 polymorphisms revealed the same pattern as that shown by meta-analysis of rs10889677. Stratification by ethnicity revealed that IL-23R gene polymorphisms were associated with CD in the Caucasian group, but not in Asians. In summary, the meta-analysis suggests a significant association between IL-23R polymorphisms and CD, especially in Caucasians.

Association between Polymorphism of Interleukin-23 Receptor and Hashimoto's Thyroiditis in Chinese Han Population of Shandong.

Objective:The interleukin-23 receptor (IL-23R) has been shown to be associated with autoimmune diseases in many different populations. This study aimed to investigate the association between IL-23R gene polymorphism and susceptibility to Hashimoto's thyroiditis (HT) in Chinese Han population of Shandong.Methods:A case–control cohort study was performed in 145 HT patients from First People's Hospital of Jining between February 2010 to October 2013 and 150 healthy controls. Two single nucleotide polymorphisms located in the promoter region of IL-23R gene (rs17375018 and rs7517847) were examined by polymerase chain reaction-restriction fragment length polymorphism analysis. Hardy-Weinberg equilibrium was performed using the Chi-square test. Genotype frequencies were estimated by direct counting, and allele and genotype frequencies between patients and controls were analyzed by the Chi-square test.Results:The rs17375018 GG genotype and the G allele were significantly increased in HT patients compared with healthy controls (P = 0.034 and P = 0.013, respectively). No association was identified between HT patients and healthy controls in rs7517847.Conclusion:The study demonstrated that polymorphism of IL-23R gene rs17375018 is highly associated with HT in Chinese Han population of Shandong, suggesting that IL-23R gene polymorphism (rs17375018 G) may play a critical role in susceptibility to HT.

Interleukin-23 Receptor Gene Polymorphism May Enhance Expression of the IL-23 Receptor, IL-17, TNF-α and IL-6 in Behcet's Disease.

PurposeRecent studies identified an association between Behcet’s disease (BD) and the IL-23R gene polymorphism (rs17375018) in different populations. This study examined whether this IL-23R gene polymorphism is associated with enhanced inflammatory responses.MethodsWe recruited 27 BD patients and 32 controls with three genotypes. Peripheral blood mononuclear cells (PBMCs) were seeded with or without anti-CD3 and CD28. Cells were incubated for 24 hours, and then supernatants were collected and stored at −20◦C until analyzed. Levels of interferon (IFN)-γ, tissue necrosis factor (TNF)-α, interleukin (IL)-17 and IL-6 were detected by ELISA. IL-23R expression was assessed by quantitative real-time polymerase chain reaction (RT-PCR).ResultsThe expression of IL-23R was significantly higher in both BD patients and healthy controls with the GG genotype compared to the AG and AA genotype with anti-CD3 and CD28 stimulation (all P-value < 0.05). Among the PBMCs cultured with anti-CD3 and CD28 stimulation, there was an elevated secretion of TNF-α, IL-6 and IL-17 in BD patients and healthy controls with the GG genotype. However, there was no significant change in secretion of IFN- γ in BD patients and healthy controls among the genotype of this IL-23R gene polymorphism.ConclusionsThe results suggest that the GG genotype of the rs17375018 variant in the IL-23R gene enhances pro-inflammatory cytokine responses.

Investigation of interleukin-12, interleukin-17 and interleukin-23 receptor gene polymorphisms in alopecia areata.

To investigate the distribution of interleukin (IL)-12 (IL12; 1188A/C), IL17 (A7488G) and IL-23 receptor (IL23R; +2199A/C) gene polymorphisms in patients with alopecia areata. Patients with alopecia areata and healthy controls were enrolled in this case-control study. Genotyping of the IL12 (1188A/C), IL17 (A7488G) and IL23R (+2199A/C) polymorphisms was undertaken. Genotype frequencies were compared between the two groups. The study enrolled 100 patients with alopecia areata and 71 control subjects. No significant differences were found in the frequencies for the IL12 and IL23R gene polymorphisms between the patient and control groups. The IL17 GG genotype was significantly more common and the IL17 GA genotype was significantly less common in patients with alopecia areata compared with controls, but only 10% of patients had the GG genotype. The IL17 GG genotype was associated with susceptibility for alopecia areata, but this genotype was only present in a small number of patients. The IL12 and IL23R gene polymorphisms were not found to have a significant association with alopecia areata.

Polymorphisms of IL-23 receptor gene are associated with susceptibility to pulmonary tuberculosis and drug-resistant pulmonary tuberculosis

To explore the associations of interleukin-23 (IL-23) receptor gene polymorphisms, susceptibility to pulmonary tuberculosis and drug-resistant pulmonary tuberculosis (TB). For this paired case-control study, 13 single nucleotide polymorphisms (SNPs) in IL-23R gene were genotyped by multiplex SNaPshot with samples from 250 pairs of culture positive pulmonary TB patients and healthy controls. And the relationship between genotype, allele, haplotype and susceptibility to pulmonary tuberculosis was analyzed. Two SNPs of IL-23R gene (rs10889677 and rs7518660) (OR = 1.53, 95% CI: 1.01-2.31; OR = 6.25, 95% CI: 3.85-10.00) were significantly associated with susceptibility to pulmonary TB and one SNP (rs11465802) (OR = 2.90; 95% CI: 1.69-4.98) was associated with drug-resistant pulmonary TB in the Chinese Uygur population. Two SNPs of IL-23R gene, rs10889677 and rs7518660, may be the risk factors of pulmonary tuberculosis. And rs11465802 may be a risk factor of drug-resistant pulmonary tuberculosis in Chinese Uygur population.

Evidence of association of interleukin-23 receptor gene polymorphisms with Egyptian rheumatoid arthritis patients

BackgroundThe identification of additional genetic risk factor is an on-going process that will aid in the understanding of rheumatoid arthritis (RA) aetiology. A genome-wide association scan in Crohn’s (CD) disease highlighted the interleukin-23 receptor (IL23R) gene as a susceptibility factor. Since the IL-23/IL-17 pathway is known to associate with other autoimmune disease, including rheumatoid arthritis and systemic sclerosis, we hypothesised that IL23R could be a shared susceptibility gene. The rare allele of IL23R single nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) confers strong protection against CD. Our aim was to analyse IL23R SNP (rs11209026, rs2201841, and rs10889677) and to detect its association with RA in Egyptian patients. MethodsA group of Egyptian patients with RA (n=120) and apparently healthy persons as controls (n=120) was genotyped for rs11209026, rs2201841 and rs10889677 by real time/polymerase chain reaction (real-time/PCR) for the first SNP and restriction fragment length polymorphism/PCR (RFLP/PCR) in the last two SNPs. ResultsOur data emphasise that the AA genotype of rs11209026 (Arg381Gln) was significantly associated with RA patients compared to the controls (P value=0.001).We did not find any significant association between either rs2201841 or rs10889677 and the development of rheumatoid arthritis (P value=1.000 & 0.562 respectively). ConclusionOur results suggest that IL23 receptor AA genotype variant of rs11209026 would contribute to RA aetiology; consequently, it might be a genetic marker for RA. We need to address the subgroup of patients who will benefit from the selective suppression of the IL23 signalling which would represent new perspectives toward a personalized therapy of RA patients by further studies.

Association of interleukin-23 receptor gene polymorphism with Behçet disease.

Behçet disease (BD) is a chronic, multisystemic disease characterized by relapsing episodes of a wide spectrum of clinical symptoms. Several genetic and immunological factors have been suggested to be involved in the aetiopathogenesis of BD. To investigate the association between BD and five single nucleotide polymorphisms (SNP) in the gene for interleukin (IL)-23 receptor (IL-23R). We recruited 123 patients with BD and 168 controls. A detailed phenotypic investigation of BD was made for each patient. Five SNPs in the IL-23R gene (rs11209026, rs7517847, rs11805303, rs1004819, rs17375018) were investigated. We found that patients with BD had a lower frequency of the rs17375018 GA and AA genotypes, and a higher frequency of the rs17375018 G allele, and these were statistically significant. The rs11209026 G allele frequency was higher in male patients with BD than in male controls, and the rs7517847G allele was higher in patients with genital ulcers. The rs11805303G and rs1004819G alleles were more frequent in patients with papulopustular lesions. The rs17375018 variant in the IL-23R gene seems likely to be a strong susceptibility factor for BD in the Turkish population. As this variant was also shown to have a higher frequency in BD patients from different ethnic backgrounds in two previous studies, it may be specific for BD.

Association of interleukin-23 receptor gene polymorphisms with risk of bladder cancer in Chinese.

To assess whether polymorphisms of the interleukin-23 receptor (IL23R) gene are associated with bladder transitional cell carcinoma because chronic inflammation contributes to bladder cancer and the IL23R is known to be critically involved in the carcinogenesis of various malignant tumors. 226 patients with bladder cancer and 270 age-matched controls were involved in the study. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. Genotype distribution and allelic frequencies between patients and controls were compared. In all three single nucleotide polymorphisms of IL23R studied, the distribution of genotype and allele frequencies of rs10889677 differed significantly between patients and controls. The frequency of allele C of rs10889677 was significantly increased in cases compared with controls (0.2898 vs. 0.1833, odds ratio 1.818, 95 % confidence interval 1.349-2.449). The result indicates that IL23R may play an important role in the susceptibility of bladder cancer in Chinese population.

Correlation between interleukin-23 receptor gene polymorphisms and risk of hepatitis B virus infection in patients

There is an increasing amount of evidence supporting the hypothesis that the pathological stage from hepatitis to hepatocellular carcinoma (HCC) is a chronic inflammatory process. Interleukin‑23 (IL‑23) is an important mediator and modulator of inflammation. Specific polymorphisms in the genes encoding subunits of the IL‑23 receptor (IL‑23R) have been consistently observed to be associated with chronic immune‑mediated diseases. In the current study, these variants were hypothesized to affect the risk of hepatitis B virus infection in patients. Three polymorphisms in the IL‑23R gene (rs10889677, rs1884444 and rs11465817) were examined in 84 cases of chronic hepatitis B (HBV), 67 cases of HBV‑related liver cirrhosis, 89 cases of HBV‑related HCC and 94 healthy controls using the polymerase chain reaction (PCR)‑restriction fragment length polymorphism method and DNA sequencing. The results revealed that subjects with the TG genotype of rs1884444 appeared to have higher susceptibility to HCC compared with the TT genotype (adjusted odds ratio (OR), 2.86; 95% confidence interval (CI), 1.39‑5.85; P=0.00). The rs1884444 G allele was associated with a significantly increased risk of HCC compared with the T allele (adjusted OR, 1.58; 95% CI, 0.96‑2.60; P=0.07). The rs11465817 and rs10889677 polymorphisms of the IL‑23R gene were not observed as being relevant to liver disease. These observations indicate that the genetic variants in the IL‑23R gene may contribute to HCC development. Additional studies with larger sample sizes must be conducted to confirm the current observations.