IL-23R Polymorphisms Research Articles

Association of Interleukin 23 Receptor Polymorphisms with Predisposition to Rheumatoid Arthritis: An Updated Meta and Trial Sequential Analysis.

The etiology of Rheumatoid Arthritis (RA) development remained unclear, and several factors, such as environmental, genetic, and immune system dysfunction, have been attributed to the susceptibility. Interleukin 23 (IL23) induces expansion of the Th17 cells through the IL-23 receptor (IL-23R) and believes in playing a major role in RA pathogenesis. Various genetic mutants in the IL23R gene (rs10489629, rs1343151, rs2201841, rs7517847, rs1004819, rs10889677, rs11209026, rs7530511) have been associated with the susceptibility RA, but results are contradictories. We performed a meta-analysis to establish the association of IL23R polymorphisms with susceptibility RA. For the meta-analysis, a detailed search of databases like Google Scholar, PubMed, Scopus, Web of Science, and Science Direct was conducted, and data were extracted from the included reports. The meta-analysis was performed by the Comprehensive Meta-Analysis v3 software. A significant association of IL-23R rs11209026 (AA vs. GG: Odds ratio = 2.250, p-value = 0.01; AA vs. GG+GA: Odds ratio = 2.271, p-value = 0.01), rs1343151 (A vs. G: Odds ratio = 1.091, p-value = 0.001; AA vs. GG: Odds ratio = 1.209, p-value = 0.001; GA vs. GG: Odds ratio = 1.116, p-value = 0.004; AA+GA vs. GG: Odds ratio = 1.135, p-value = 0.000; AA vs. GG+GA: Odds ratio = 1.144, p-value = 0.012) and rs10889677 (CA vs. CC: Odds ratio = 1.375, p-value = 0.041) polymorphisms were observed with increased susceptibility for the development of RA. In contrast, IL-23R rs10489629 (G vs. A: odds ratio = 0.901, p-value = 0.047, GG vs. AA: Odds ratio = 0.763, p-value = 0.022, GG vs. AA+AG: Odds ratio = 0.852, p-value = 0.00) and IL23R rs2201841 (CC vs. TT+TC: Odds ratio = 0.826, p-value = 0.026) variants were linked with protection against the development of RA. In addition, the trial sequential analysis revealed the inclusion of a sufficient number of studies in the present meta-analysis, and no further additional studies are required. IL-23R variants are associated with genetic susceptibility or resistance against the development of RA.

Association between a single nucleotide polymorphism of the IL23R gene and tuberculosis in a Chinese Han population: a case‒control study

BackgroundSevere tuberculosis constitutes a significant menace to human safety and well-being, with a considerable mortality rate. The severity of tuberculosis can be impacted by genetic variations in host genes, particularly single nucleotide polymorphisms (SNPs).MethodsA case‒control study was undertaken, encompassing a cohort of 1137 tuberculosis patients (558 with severe tuberculosis and 579 with mild tuberculosis), alongside 581 healthy controls within the age range of fifteen to forty-five years. Whole blood DNA was extracted from all participants, and three tag polymorphisms (rs1884444, rs7518660, rs7539625) of the IL23R gene were selectively identified and genotyped.ResultsNo significant correlation was observed between the IL23R gene polymorphisms (rs1884444, rs7518660, and rs7539625) and tuberculosis. Upon comparing the tuberculosis group with the healthy control group, the mild tuberculosis group with the healthy control group, and the severe tuberculosis group with the healthy control group, the obtained P-values were> 0.05. However, in the comparison between severe tuberculosis and mild tuberculosis, the presence of rs1884444 G alleles exhibited a significantly increased risk of severe tuberculosis after adjusting for age and sex (ORa: 1.199, 95% CI: 1.009–1.424; Pa=0.039, respectively). In subgroup analysis, after accounting for confounding factors, including age and sex, rs1884444 G alleles continued to demonstrate a significantly heightened risk of severe tuberculosis. Nonetheless, the comparison between the multisystemic tuberculosis group and the mild tuberculosis group was no significant difference. Notably, rs1884444 of the IL23R gene exhibited a noteworthy association with the risk of severe tuberculosis in the comparison between severe tuberculosis and mild tuberculosis before and after adjusting for age and sex (ORa: 1.301, 95% CI: 1.030–1.643; Pa=0.027, respectively). Furthermore, the presence of the rs1884444 G allele exhibited a significantly increased risk of severe tuberculosis after adjusting for age and sex in the comparison between tuberculous meningitis and mild tuberculosis (ORa: 1.646, 95% CI: 1.100-2.461; Pa=0.015, respectively).ConclusionsThe present study suggests that there is no significant association between IL23R gene polymorphism and tuberculosis susceptibility in the Chinese Han population. However, it does indicate a potential link between IL23R polymorphism and an increased risk of developing severe tuberculosis.

Suggestive evidence of genetic association of IL23R polymorphisms with chronic obstructive pulmonary disease risk in the Chinese population.

Chronic obstructive pulmonary disease (COPD) is a worldwide public health problem. Previous genetic association studies have identified several susceptibility loci in the interleukin genes that may participate in the nosogenesis of COPD. This study aimed to evaluate the relationship between IL23R loci and COPD susceptibility in the Chinese population. Agena MassARRAY technology was applied to genotype five single nucleotide polymorphisms (SNPs) in the IL23R gene in 498 COPD patients and 498 healthy people. The association between IL23R SNPs and COPD risk was calculated by logistic regression analysis, with odds ratios and 95% confidence intervals. The false-positive report probability analysis was noteworthy for evaluating the significant results. Also, haplotype analysis was performed among IL23R variants, and multifactor dimensionality reduction analysis was performed to assess the SNP-SNP interactions to predict the risk of COPD. Overall analysis showed that rs7517847 had a significant association with an increased risk of COPD. Age-stratified analysis revealed that rs7517847 was significantly related to an increased risk of COPD in people aged over 68 years old. Sex-stratified analysis illustrated a significant association between rs2295359 and rs7517847 and COPD risk in the female population. The significant association of COPD risk with IL23R SNPs was assessed by false-positive report probability values. Additionally, we observed that the haplotypes AAC and GGA formed by rs2201841, rs12743974 and rs10889677 were associated with a reduced risk of COPD (p = 0.009, p = 0.026). Also, the five-loci interaction model formed by rs2295359, rs7517847, rs2201841, rs12743974 and rs10889677 became the best predictor of COPD, with 10/10 cross-validation consistency and 52.4% testing balance accuracy. The research indicated a remarkable association between IL23R variants and COPD susceptibility in the Chinese population. Larger samples and functional research are required to ascertain the relationship between IL23R variants and COPD susceptibility.

Single nucleotide polymorphisms in ADAM17, IL23R and SLCO1C1 genes protect against infliximab failure in adults with Crohn’s disease

BackgroundTo predict primary failure of infliximab (IFX) therapy in Crohn’s disease (CD) and to identify patients who maintain long-term effectiveness to IFX is currently not feasible. Some genetic variations are proposed as potential biomarkers. AimWe assessed a set of single nucleotide polymorphisms (SNPs) in genes related to the IFX mechanism of action and the presence of HLA-DQA1 * 05 allele on the primary response and long-term durability in CD patients. MethodsA multi-centre cross-sectional study of IFX-exposed adult patients with CD was undertaken. Treatment persistence and time to failure were co-primary endpoints. DNA from the 131 patients was genotyped. Association between SNPs and clinical variables with IFX persistence was assessed. ResultsFailure to IFX was documented in 65 (49.6%) out of 131 patients. IFX persistence was associated either with carrying the TT genotype in ADAM17 rs10929587 (ORa=0.2; 95%CI=0.1–0.8; p = 0.021), or the CC genotype in SLCO1C1 rs3794271 (ORa=0.2; 95%CI=0.1–0.7; p = 0.008), according to multivariate logistic regression. In contrast, previous bowel resection increased the risk of IFX failure (ORa=2.8; 95%CI=1.1–7.3; p = 0.025). Cox regression analysis confirmed these findings and also identified IL23R rs10489629-TT (HRa 0.41; 95%CI=0.22–0.75; p = 0.004) and concomitant immunosuppressants (HRa 0.46; 95%CI=0.27–0.77; p = 0.003) as protection from IFX failure. However, no association between HLA-DQA1 * 05 allele and persistence of IFX therapy was found, with similar failure rates among carriers and non-carriers (52.8% vs. 47.4%, respectively; p = 0.544). ConclusionsSNPs rs10929587-TT in ADAM17, rs10489629-TT in IL23R and rs3794271-CC in SLCO1C1, together with no previous bowel surgery and concomitant immunosuppression, were identified as protection from failure to IFX.

Investigation of the Relationship between IL-6, IL-6R and CXCL5 Polymorphisms and Obesity in Denizli Province of Turkey

Obesity and its effects on increasing morbidity and mortality have reached the level of an epidemic with a high frequency in modern populations. IL-6 released from adipose tissue is known to trigger the chronic inflammation in obesity. CXCL5, which mediates the activation and migration of neutrophils, has been found at high levels in obese subjects. In our study, we aimed to investigate the possible effects of IL-6, IL-6R and CXCL5, polymorphisms and haplotypes on the development of obesity. We studied IL-6, rs2069827 (-1363, G/T), rs1800797 (-597, G/A), rs1800796 (-572, G/C) and rs1800795 (-174, G/C), IL-6R rs4845617 (-183, G/A), rs2228145 (+48892, A/C) and CXCL5 rs352046 (-156, G/C) polymorphic sites in 60 obesity patients and 59 healthy controls. For genotyping we used PCR-RFLP based approach. The IL-6 rs1800796, rs1800795 and IL-6R rs4845617 G allelles could be the possible genetic factors responsible for obesity. We found similar results in female obese group. The results indicated that there was no association between obesity and other SNPs (rs2069827, rs1800797, and rs1800795 and rs2228145) and CXCL5, rs352046. The results of IL-6 and IL-6R haplotype analysis by global differentiation test showed that haplotypes may have different distributions between obese and controls. Our results showed that polymorphisms and possible haplotypes in IL-6 and IL-6R genes, which have an important role in inflammation, may affect the development of obesity. This study points out the necessity of investigating the possible effects of gene polymorphisms of other cytokines and their receptors in the development of obesity in larger populations.

IL6R gene polymorphisms and their relation to chronic obstructive pulmonary disease susceptibility in theChinese population.

Background: This work was designedto explore the correlation between IL6R polymorphisms and chronic obstructive pulmonary disease (COPD) susceptibility. Methods: Agena MassARRAY was used to genotype five SNPsof IL6R in 498 patients with COPD and 498 controls. Genetic models and haplotype analysis were used to assess the associations between SNPs and COPD risk. Results: Rs6689306 and rs4845625 increase the risk of COPD. Rs4537545, rs4129267 and rs2228145 were related to a decreased risk of COPD in different subgroups. Haplotype analysis revealed that GTCTC, GCCCA and GCTCA contributed to a reduced risk of COPD after adjustment. Conclusion: IL6R polymorphisms are significantly associated with COPD susceptibility.

Genetic association of IL2RA, IL17RA, IL23R, and IL31RA single nucleotide polymorphisms with alopecia areata

The signalling of cytokine receptors plays a crucial role in regulating tolerance and immunity. Impaired immunological processes result in autoimmune inflammation that target the hair follicles, causing many hair disorders, mainly alopecia areata (AA). Therefore, polymorphisms in cytokine receptor genes are suggested to have a significant impact on the pathogenesis of AA, a disease with a multifactorial basis and uncertain etiology. In the present study, 152 AA patients of the Jordanian population were investigated for their genetic susceptibility to develop AA compared to 150 control subjects. Genomic DNA extraction and genotyping had conducted forIL17RA(rs879575, rs2229151, and rs4819554),IL2RA(rs3118470),IL23R(rs10889677), andIL31RA(rs161704) using the Sequenom MassARRAY® system. The allele frequency ofIL17RArs879575 is significantly higher in patients, while no statistical differences were found forIL2RA, IL23R,andIL31RASNPs. Also, the recessive model ofIL31RArs161704 showing that AA genotype is significantly associated with AA development. To date, there is no published data regarding the association between AA and the selected genetic variants in our population. However, this study's findings assert that SNPs ofIL17RAandIL31RAare linked to AA susceptibility in Jordanian patients.

Diyabetik Periferik Polinöropatili Hastalarda İnterlökin-23R Gen Polimofizmleri

Objective: Proinflammatory and neurovascular changes are blamed in the pathogenesis of diabetic neuropathy. Although it is accepted that diabetes is a trigger for vascular inflammation, it has been suggested that inflammation itself may trigger diabetes. Interleukin-23 (IL-23) is a pro-inflammatory cytokine secreted by activated macrophages and dendritic cells. Interleukin-23R is known to have a critical role in chronic inflammatory diseases. The aim of this study is to determine the relationship between IL-23R polymorphism and diabetic peripheral neuropathy.
 Method: 50 diabetic peripheral neuropathy patients who applied to Neurology outpatient clinic, and 52 healthy controls compatible with the patient group in terms of age and gender were included. Electromyography was performed on all of the volunteers, who agreed to participate in the study, and 2 ml of blood samples were taken into tubes with EDTA, and the IL-23R gene polymorphism was analyzed using the pyrosequencing method.
 Results: IL-23R gene variants rs2201841, rs199542433, rs201052419, rs11209026 were analyzed in diabetic peripheral neuropathy (DPN) patients and control group. While we investigate IL23R polymorphisms we didn’t find any significant differences between patient and control groups. But when we use odds ratios, rs2201841 seems to have a protective role, and rs199542433 in both dominant and recessive models and rs11209026 only recessive model seem to be related 10 fold higher risks for DPN.
 Conclusion: IL-23R gene polymorphism has been shown to be associated with many autoimmune and inflammatory diseases. It is known that inflammation has an important effect on diabetes. The frequency of IL-23R gene polymorphism was not significant in diabetic peripheral neuropathy. Our study is the only and first study investigating the role of IL-23R gene polymorphism in diabetic peripheral neuropathy. Ethnicity is very important in genetic studies, and it will give us more clear information for the future to carry out this study in patients with other ethnic origins and to recruit larger study groups.

Associations between IL-23R gene polymorphism (rs10889677 A/C) and ankylosing spondylitis and rheumatoid arthritis susceptibility: A meta-analysis with trial sequential analysis

Objectives Autoimmune diseases are a kind of chronic diseases for which the immune system loses tolerance to autoantigens. This meta-analysis’ purpose is to determine whether there exists a correlation between IL-23R polymorphism and common autoimmune diseases like ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Methods We searched the relevant literatures up to September 2021 and used different effect models for meta-analysis. 95% confidence interval (95% CI) and odds ratio (OR) were used to determine the relationship between rs10889677 (A/C) polymorphism and AS as well as RA. Finally, to promote the reliability of results, the trial sequential analysis (TSA) has also been applied and we searched the data related to autoimmune diseases (AS, RA) on genome-wide association studies (GWAS). Results Generally, 31 studies were included. Rs10889677 (A/C) was significantly correlated with the susceptibility to AS and RA among the general individuals (p < .05). Moreover, there existed a relevance between allele A and AS as well as RA in Caucasians (p < .05). AA genotype increased the risk of autoimmune diseases in Mongolians. As a result, the robustness of meta-analysis has further been proved by TSA. Conclusion IL-23R (rs10889677 A/C) A allele was a risk gene for AS and RA in the general population, especially in Caucasians. AA genotype increased the risk of AS and RA in Mongolians.

Associations of IL-4, IL-4R, IL-17A, and IL-17F Polymorphisms with Colorectal Cancer Risk: A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis.

Both interleukin (IL)-4 and IL-17 polymorphisms may be involved in the pathogenesis and progression of colorectal cancer (CRC). Herein, we designed a meta-analysis to assess the associations between IL-4, IL-4R, IL-17A, and IL-17F polymorphisms and CRC risk. Scopus, Web of Science, Cochrane Library, and PubMed databases were searched to retrieve articles published until October 21, 2021. We used crude odds ratio (OR) and 95% confidence interval assessing the association of the polymorphisms and CRC risk in 5 genetic models. Trial sequential analysis for the primary analyses was used to control random errors. Twenty-three studies (8: IL-4 rs2243250, 4: IL-4R rs1801275, 5: IL-17A rs2275913, and 6: IL-17F rs763780) were involved in the meta-analysis. The pooled OR (P-value) for the association between IL-4 rs2243250 polymorphism and the CRC risk was 1.11 (0.08), 1.27 (0.12), 1.07 (0.37), 1.09 (0.17), and 1.22 (0.12), for IL-4R rs1801275 polymorphism was 0.71 (0.18), 1.05 (0.76), 0.86 (0.37), 0.87 (0.41), and 0.69 (0.39), for IL-17A rs2275913 polymorphism was 1.83 (0.0003), 1.73 (0.06), 1.47 (<0.001), 1.61 (0.001), and 1.42 (0.15), and for IL-17F rs763780 polymorphism was 1.07 (0.48), 5.33 (0.02), 1.08 (0.49), 1.08 (0.47), and 8.42 (0.002) in allelic, homozygous, heterozygous, recessive, and dominant models, respectively. The G allele and GA genotype of IL-17A rs2275913 polymorphism and the CC genotype of IL-17F rs763780 polymorphism had an elevated risk in CRC cases. The ethnicity and genotyping method, sample size, control, and publication year were effective factors on the pooled results.

Association between interleukin 12B and interleukin 23R gene polymorphisms and systemic lupus erythematosus: a meta-analysis.

ObjectiveTo determine whether polymorphisms of interleukin 12B (IL12B) and IL23 receptor genes (IL23R) confer susceptibility to systemic lupus erythematosus (SLE).MethodsA meta-analysis was conducted to analyze the associations between SLE and IL12B rs3212227 and rs17860508 and IL23R rs7517847, rs10489629, rs10889677, rs1004819, rs11209026, rs11209032, rs1343151, and rs1884444 polymorphisms using allele contrast, dominant, recessive, heterozygote, and homozygote models. Ten studies involving 1989 patients with SLE and 2394 controls were considered for the meta-analysis.ResultsThe meta-analysis using the homozygote model revealed that IL23R rs10889677 was significantly associated with SLE susceptibility in the overall population (AA vs. CC) (odds ratio = 0.70, 95% confidence interval = 0.50–0.98) but not in the Asian population. Other polymorphisms of IL12B and IL23R were not significantly associated with SLE protection.ConclusionsThese findings suggest that the IL23R rs10889677 polymorphism confers SLE susceptibility to individuals of certain ethnicities. (Research Registry number: 1268)

Association of genetic polymorphisms in IL-23R and IL-17A with the susceptibility to IgA nephropathy in a Chinese Han population.

IgA Nephropathy (IgAN) is one of the most common causes of chronic kidney damage worldwide. Identifying new genetic factors associated with IgAN risk is of invaluable importance. To explore the association between polymorphisms of IL-23R and IL-17A and the susceptibility of IgAN, 164 IgAN patients and 192 healthy controls were genotyped for five SNPs in a Chinese Han population. A comparative analysis between genotype distributions, clinical indexes and pathological grades in the IgAN patients was also performed. The GG genotype and a G allele of rs7517847 were associated with a decreased IgAN risk (OR: 0.545; 95% CI: 0.299-0.993; p = 0.046; OR: 0.730; 95% CI: 0.541-0.984; p = 0.039) compared to the TT genotype and T allele respectively. Furthermore, the AA genotype of rs2275913 appeared to reduce the IgAN risk (OR: 0.405; 95% CI: 0.209-0.786; p = 0.007) compared to the GG genotype. Consistently, individuals harboring an AA genotype had a lower IgAN risk (OR: 0.380; 95% CI: 0.211-0.686; p = 0.001) under the recessive model. Our study demonstrated for the first time the significant associations of rs7517847 in IL-23R and rs2275913 in IL-17A with the risk of IgAN in Chinese Han.

Genetic association study of NOD2 and IL23R amino acid substitution polymorphisms in Saudi Inflammatory Bowel Disease patients

BackgroundInflammatory Bowel Disease (IBD) is a complex autoimmune disease whose genetic basis is not well explored in the highly consanguineous Saudi population. Therefore, this study aims to evaluate the relevance of NOD2 and IL23R genes polymorphisms, selected from Caucasian Genome-wide association study (GWAS) findings, as risk markers for IBD pathology in Saudi patients. Materials and MethodsThe genetic status of NOD2 and IL23R polymorphisms of 97 IBD patients and 100 healthy individuals was determined through real-time PCR based TaqMan Allelic Discrimination Assay. Genotype calls of TaqMan assay were further validated by the direct DNA sequencing method. The pathogenicity of the variants was further explored by computational predictions and by 3D structural modelling methods. ResultsOur study found no evidence for a significant association of Caucasian IBD risk alleles, i.e., NOD2 (P268S and R702W) and IL23R (G149R and R381Q) with IBD pathology in Saudi Arabian patients under dominant, recessive or co-dominant genetic models. Moreover, SNP-SNP interaction analysis with multidimensionality reduction assays have also confirmed the above findings. Our computational predictions of the variants suggest the variable deleterious nature and minor structural drifts on the tertiary protein structures. ConclusionThis study expands the genetic heterogeneity of IBD and concludes that Caucasian genetic risk markers have limited or of no use in estimating the risk of IBD development in Saudi patients. Future genetic association studies in Saudi Arabia need to employ genetic markers whose minor allele frequencies exceed 10% in Arab population to have robust outcomes.

Allergies, genetic polymorphisms of Th2 interleukins, and childhood acute lymphoblastic leukemia: The ESTELLE study.

A negative association between a history of allergy and childhood acute lymphoblastic leukemia (ALL) has been reported in previous studies, but remains debated. This work aimed to investigate this association accounting for genetic polymorphisms of the Th2 pathway cytokines (IL4, IL10, IL13, and IL4R). Analyses were based on the French case-control study ESTELLE (2010-2011). The complete sample included 629 ALL cases and 1421 population-based controls frequency-matched on age and gender. The child's medical history was collected through standardized maternal interview. Biological samples were collected, and genotyping data were available for 411 cases and 704 controls of European origin. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders. In the complete sample, a significant inverse association was observed between ALL and reported history of allergic rhinitis or sinusitis (OR=0.65 [0.42-0.98]; P=0.04), but there was no obvious association with allergies overall. There was an interaction between genetic polymorphisms in IL4 and IL4R (Pinteraction = 0.003), as well as a gene-environment interaction between IL4R-rs1801275 and a reported history of asthma (IOR=0.23; Pint =0.008) and eczema (IOR=0.47; Pint =0.06). We observed no interaction with the candidate polymorphisms in IL4 and IL13. These results suggest that the association between allergic symptoms and childhood ALL could be modified by IL4R-rs1801275, and that this variant could also interact with a functional variant in IL4 gene. Although they warrant confirmation, these results could help understand the pathological mechanisms under the reported inverse association between allergy and childhood ALL.

CCR6, IL7R, FAS and Madcam-1 Single Nucleotide Polymorphisms Are Associated with Higher Incidence of Infections in Allogeneic Stem-Cell Transplant from a Related Donor after a Reduced Intensity Conditioning Regimen: A Multicenter Experience

INTRODUCTION: Infection complications are important cause of morbidity and non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-SCT), even in HLA-identical sibling donors. Although there are many studies associating single nucleotide polymorphisms (SNPs) and allo-SCT evolution, these are mainly related with graft versus host disease (GVHD) and/or transplant related mortality (TRM), with few focused on post-allo-SCT infections. This multicentric study analyzes the potential implication of SNPs with cytomegalovirus (CMV) reactivation and fungal infection (FI) development in allo-SCT with reduced intensity conditioning (RIC).MATERIALS AND METHODS: We included paired recipient-donor samples from 247 RIC allo-SCT for patients diagnosed of AML (35%), NHL (21%), MDS (16%), MM (10%), CLL (7%), HL (6%), or others (5%) in four centers in Spain. Flu-Bu conditioning was used in 55% of the transplants while Flu-Mel in 42%. A total of 52 SNP were analyzed from 44 different gene loci and genotyping was carried out by Sequenom Mass ARRAY platform. Allele frequencies were estimated by direct counting and compared between groups using Fisher's test. P-value <0.05 was considered to be statistically significant. Log-rank analysis was used to compare differences between survival curves.RESULTS: Patient's characteristics are shown in Table 1. The median follow up for patients was 28 months (1-175), overall survival at 5 years was 45%, while the event-free survival at 5 years was 57%. Cumulative incidence of CMV reactivation at 3 years was 34% and of FI 11%. Transplant related mortality was 17%, and infection related mortality 14%.In univariate analysis, patients with genotype A/A in rs3093023 (CCR6) showed a lower incidence of CMV reactivation (table 2), along with acute GVHD were the variables associated in multivariate analysis.Regarding to FI, recipient genotype A/A in rs1494555 (IL7R), donor C/C in rs1800795 (FAS), and donor G/G in rs2302217 (MAdCAM-1) were associated with higher FI incidence (table 2), being the only variables related in multivariate analysis.CONCLUSION: This data suggest an association between rs3093023 (CCR6), rs1494555 (IL7R), rs1800795 (FAS) and rs2302217 (MAdCAM-1) polymorphisms with higher incidence of post-allo-SCT opportunist infection. Confirmation in larger series is required.FUNDING: RD12/0036/0069, CB16/12/00233 and 00480, PI12/02361 and ERDF, Innocampus; CEI-2010- 1-0010 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Gene Polymorphisms of NOD2, IL23R, PTPN2 and ATG16L1 in Patients with Crohn's Disease: On the Way to Personalized Medicine?

Genetic and environmental factors are involved in the pathogenesis of inflammatory bowel diseases (IBD). The study aimed at investigating the potential influence of single nucleotide polymorphisms (SNPs) NOD2 rs2066844, NOD2 rs2066845, NOD2 rs2066847, IL23R rs11209026, PTPN2 rs2542151, PTPN2 rs7234029, and ATG16L1 rs2241880 on the response to immunomodulatory therapies and disease course in Crohn’s disease (CD). This is an uncontrolled retrospective monocentric study including patients from the IBD outpatient clinic of Heidelberg University Hospital. Therapy responses and disease courses were related to genetic findings. 379 patients with CD were included. The presence of at least one PTPN2 rs7234029 risk allele was associated with nonresponse to anti-interleukin-12/23 treatment (89.9% vs. 67.6%, p = 0.005). The NOD2 rs2066844 risk allele was associated with a first-degree family history of colon cancer (12.7% vs. 4.7%, p = 0.02), the ATG16L1 rs2241880 risk allele with ileal CD manifestation (p = 0.027), and the IL23R rs11209026 risk allele with a higher rate of CD-related surgeries per disease year (0.08 vs. 0.02, p = 0.025). The results of this study underline the relevance of genetic influences in CD. The association of the PTPN2 rs7234029 risk allele with nonresponse to anti-interleukin-12/23 treatment in CD patients is a novel finding and requires further investigation.

Polymorphisms of interleukin 4 and interleukin 4 receptor genes and bronchial asthma risk among Egyptian children

BackgroundInterleukin 4 (IL4) is a key cytokine that regulates the inflammatory cascade in bronchial asthma. We investigated the association between the IL4 and IL4R polymorphisms and the susceptibility for bronchial asthma among Egyptian children. MethodsIL4 VNTR and IL4R c.1902 A>G p.(Q576R) polymorphisms were investigated among 100 children with bronchial asthma and 100 healthy controls using PCR method. Serum levels of IL4 and immunoglobulin E (IgE) were assessed by ELISA. ResultsThe frequencies of (A1A2 + A2A2) genotypes and A2-allele of the IL4 VNTR variant were significantly higher among asthmatic patients than controls (p = 0.01, OR = 2.34, 95% CI = 1.24–4.44; p = 0.01, OR = 2.27, 95% CI = 1.29–3.99, respectively). The frequencies of (AG + GG) genotypes and G-allele of the IL4R (A1902G) variant were significantly higher among asthmatic patients than controls (p = 0.003, OR = 2.52, 95% CI = 1.39–4.58; p = 0.002, OR = 2.25, 95% CI = 1.35–3.76, respectively). There was a significant association between (A1A2 + A2A2) genotypes of the IL4 VNTR variant and high serum IL4 level among asthmatic patients (p < 0.001). The (AG + GG) genotypes of the IL4R (A1902G) variant were significantly associated with exposure to triggers, atopic dermatitis and higher serum IgE level in asthmatic patients (p = 0.02, 0.04 and 0.01, respectively). ConclusionIL4 VNTR and IL4R (A1902G) polymorphisms could be associated with higher risks of bronchial asthma among Egyptian children.

TH17/IL23 cytokine gene polymorphisms in bullous pemphigoid.

BackgroundTH17/IL‐23 immune axis is considered to be involved in the pathogenesis of autoimmune and chronic inflammatory diseases. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease, characterized by the presence of autoantibodies against the components of the dermal‐epidermal junction. Animal studies and characterization of patient samples point toward a contribution of TH17 cells in BP pathogenesis. However, genetic polymorphisms in the genes of TH17/IL‐23 cytokines have not yet been well investigated in BP.MethodsDetection of polymorphisms in IL‐17A (rs2275913 and rs3819025), IL‐17F (rs2397084 and rs763780), IL‐17RA (rs2229151), and IL‐23R (rs2201841, rs7530511, rs11209026, and rs10889677) genes were performed following the collection of blood samples and DNA extraction from BP patients and controls. Gene expression of IL‐23R was determined by quantitative RT‐PCR analysis.ResultsThe prevalence of IL‐23R rs7530511 genotypes and alleles, as well as IL‐23R rs2201841 alleles, is significantly different between the BP patients and controls. While the minor C‐allele of IL‐23R rs7530511 is highly present in the patients, the G‐allele distribution of IL‐23R rs2201841 is significantly more prevalent in the control individuals compared to the BP patients. Genotypes and alleles of other SNPs in IL‐17A, IL‐17F, and IL‐17RA were similarly distributed in patients and controls.ConclusionsNo alteration was found in the gene expression between wild and polymorphic genotypes of IL‐23R (rs2201841 and rs7530511) variations, indicating they do not contribute to altering the levels of gene expression in blood. In summary, our data show that the alleles of two SNPs in IL‐23R rs2201841 and rs7530511 are associated with BP.

The Association Study of IL-23R Polymorphisms With Cerebral Palsy in Chinese Population.

Background: Cerebral palsy (CP) is a syndrome of non-progressive motor dysfunction caused by early brain development injury. Recent evidence has shown that immunological abnormalities are associated with an increased risk of CP.Methods: We recruited 782 children with CP as the case group and 770 healthy children as the control group. The association between IL-23R single nucleotide polymorphisms (SNPs; namely, rs10889657, rs6682925, rs1884444, rs17375018, rs1004819, rs11805303, and rs10889677) and CP was studied by using a case–control method and SHEsis online software. Subgroup analysis based on complications and clinical subtypes was also carried out.Results: There were differences in the allele and genotype frequencies between CP cases and controls at the rs11805303 and rs10889677 SNPs (Pallele = 0.014 and 0.048, respectively; Pgenotype = 0.023 and 0.008, respectively), and the difference in genotype frequency of rs10889677 remained significant after Bonferroni correction (Pgenotype = 0.048). Subgroup analysis revealed a more significant association of rs10889677 with CP accompanied by global developmental delay (Pgenotype = 0.024 after correction) and neonatal encephalopathy (Pgenotype = 0.024 after correction).Conclusion: The present results showed a significant association between IL-23R and CP, suggesting that IL-23R may play a potential role in CP pathogenesis.

Determine the Effect of Polymorphisms of and IL23R Genes on in Psoriasis in Babylon Province

Background: IL23R Polymorphisms appear to be engaged with several different types of autoimmunediseases such as psoriasis.Aim: We investigated the association of the Arg381Gln (R381Q) polymorphism in the IL23R gene withpsoriasis risk in Babylon province.Methodology: The IL23R-gene variation Arg381Gln (R381Q) was performed using the programmablethermal cycler gradient PCR system. We investigated the association of IL23R gene variants with differentclinic pathological features of psoriasispatients.Results: The allelic frequency of IL-23R Arg381Gln (R381Q) (rs11209026) gene showed that the frequencyof AA genotype in patients with Psoriasis was more than in the control group (13 vs 8%) (OR = 2.222, CI95% (0.476-10.357). In addition, this study suggests there is a statistical difference (P-valu&gt;0.05) between(AG) and (AA) (P-value = 0.033),(AG) and (GG) (P-value = 0.012) genotypes in patients group compared tocontrols. The results also showed that the frequency of (G) Arg allele was (0.6) (0.62) in patients and controlgroup respectively, and found no significant difference between (A) Gln and (G) Arg alleles in patients andcontrols (OR= 0.754), CI 95% (0.42-1.22).Conclusion: Our results showed no significant association of the IL-23R Arg381Gln (R381Q) (rs11209026)polymorphism with psoriasis patients susceptibility in Babylon province. The IL-23R Arg381Glnheterozygoteno significantly increases the risk and can’t be useful as a predisposing genetic marker.