IL18 polymorphism is associated with Behcet's disease but not lupus in patients from Turkey.
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ABSTRACT:
SUBMITTER: Htoon J
PROVIDER: S-EPMC3102261 | biostudies-literature | 2011 May
REPOSITORIES: biostudies-literature
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IL18 polymorphism is associated with Behçet's disease but not lupus in patients from Turkey.
Htoon Jasmine J Nadig Ajay A Hughes Travis T Yavuz Sule S Direskeneli Haner H Saruhan-Direskeneli Güher G Sawalha Amr H AH
The Journal of rheumatology 20110501 5
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Project description:The Behçet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors. HLA types were imputed from single nucleotide polymorphism genotypes determined with the Immunochip. The presence of inhibitory KIR3DL1 or activating KIR3DS1 alleles did not differ significantly between cases and controls (KIR3DL1: 92.9% vs 93.4%, Pdominant=0.55; KIR3DS1: 42.7% vs 41.0%, Pdominant=0.29). The KIR3DL1/KIR3DS1 alleles were also present at similar frequencies among cases and controls bearing HLA-B with a Bw4 motif; HLA-B with a Bw4 motif with isoleucine at position 80; and HLA-B*51. Our results suggest that pathogenic mechanisms associated with HLA-B*51 do not primarily involve differential interactions with KIR3DL1 and KIR3DS1 receptors. However, due to the complexity of this locus (that is, sequence variation and copy number variation), we cannot exclude a role for other types of KIR variation in the pathogenesis of BD.
| S-EPMC5590678 | biostudies-literature
Project description:Behçet's disease (BD) is an autoimmune multisystemic disease. The precise etiology of BD is not fully understood; however, it is thought that interactions between genetic and environmental factors play an essential role in its pathogenesis. The nuclear receptor coactivator-5 (NCOA5) gene encodes a coregulator for nuclear receptor subfamily 1 group D member 2 (NR1D2) and estrogen receptor 1 and 2 (ESR1 and ESR2). Also, the NCOA5 gene insufficiency leads to an elevated expression of IL-6, and increased levels of IL-6 were found to be related to the pathogenesis of BD. In this study, we aimed to clarify the impact of the NCOA5 rs2903908 polymorphism on susceptibility and clinical findings of BD. This study included 671 participants (300 BD patients and 371 healthy controls). The analyses of NCOA5 rs2903908 polymorphism was performed by using the TaqMan allelic discrimination assay. The frequency of TT genotype of the NCOA5 rs2903908 polymorphism was found significantly higher in BD patients compared to those in healthy controls (p=0.016, OR=1.46, 95 % CI=1.08-1.99). Also, the frequencies of CT genotype was observed significantly higher in BD patients with genital ulceration and uveitis than without genital ulceration and uveitis (p=0.002 and p=0.005, respectively). The most significant association was found between C allele frequencies of BD patients with and without uveitis (p=0.0001). Our study represents for the first time that the NCOA5 rs2903908 polymorphism seemed to be linked to BD susceptibility and clinical findings.
| S-EPMC5491927 | biostudies-literature
Project description:BackgroundThe diagnosis of Behçet's disease (BD) remains challenging due to the lack of diagnostic biomarkers. This study aims to identify potential serum metabolites associated with BD and its disease activity.MethodsMedical records and serum samples of 24 pretreated BD patients, 12 post-treated BD patients, and age-matched healthy controls (HC) were collected for metabolomics and lipidomics profiling using UPLC-QTOF-MS and UPLC-QTOF-MSE approaches. Additionally, serum samples from an independent cohort of BD patients, disease controls including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Takayasu's arteritis (TA), Crohn's disease (CD) patients, and HC were collected for further validation of two potential biomarkers using UPLC-QTOFMS analysis.ResultsUnsupervised principal component analysis (PCA) showed a clear separation of metabolomics profiles of BD patients from HC. Statistical analysis of the data revealed differential metabolites between BD patients and HC. The serum levels of some phosphatidylcholines (PCs) were found to be significantly lower in BD patients, while the levels of several polyunsaturated fatty acids (PUFAs) were increased markedly in the BD group compared with HC. Furthermore, the serum level of two omega-6 PUFAs, linoleic acid (LA) and arachidonic acid (AA), were dramatically decreased in patients with remission. A validation cohort confirmed that the serum LA and AA levels in BD patients were significantly higher than those in HC and patients with RA, SLE, TA, and CD. In addition, receiver operating characteristic (ROC) analysis indicated good sensitivity and specificity.ConclusionsThe serum metabolomics profiles in BD patients are altered. Serum LA and AA are promising diagnostic biomarkers for BD.
| S-EPMC6154820 | biostudies-literature
Project description:The allergic asthma phenotype is characterized by a T helper type 2 (Th2) immune response, based on Immunoglobulin E (IgE)-mediated type 1 hypersensitivity reactions. Total IgE is the sum of all IgE types produced by the human body and is used as a biomarker of inflammation in asthma. We analysed data collected in 143 asthma cases (median age 42.1 years) from the general Italian population (GEIRD survey; 2008-2010) to identify single nucleotide polymorphisms (SNPs) in candidate genes that are associated with total IgE in adult subjects with asthma. These patients reported respiratory symptoms in response to perennial allergens and provided data on 166 SNPs tagging 50 candidate genes or gene regions. Replication of the statistically significant results was performed in 842 asthma cases from other European countries (ECRHS II survey; 1998-2002). SNP rs549908 in interleukin 18 (IL18) gene was significantly associated with total IgE in GEIRD, and this result was replicated in ECRHS II. SNP rs1063320 in the human leukocyte antigen G (HLA-G) gene was identified in GEIRD, but this association was not replicated in ECRHS II. Further investigating IL18 and its biological pathways could be important for developing new therapeutic targets, due to its involvement in inflammatory response processes.
| S-EPMC10299306 | biostudies-literature
Project description:BackgroundSeveral studies suggested the genetic association between IL10RA variants and susceptibility to Behcet's disease (BD). However, the precise mechanism of the association is still unknown. The purpose of this study was to investigate the mechanism underlying the genetic associations between IL10RA polymorphisms and the risk of BD.MethodsTo analyse the genetic susceptibility to BD mediated by IL10RA causal polymorphisms, we performed a study on data from our previous genome-wide association studies (GWAS), the bioinformatic analysis of post-annotation of GWAS and relevant mechanism verification experiments, including chromatin immunoprecipitation, luciferase gene-reporter assay, electrophoretic mobility shift assays, and enzyme-linked immunosorbent assay.ResultsAmong 125 single nucleotide polymorphisms (SNPs) with P < 1 × 10-5 identified in our previous GWAS study on BD, rs4936415 (G/C) was predicted with the highest conserved score as an expression quantitative-trait-locus SNP for IL10RA in whole blood. There were H3K27ac and H3K4Me1 enhancer-specific enrichments around SNP rs4936415. Luciferase gene-reporter assays revealed that the rs4936415 G-allele construct showed a higher enhancer activity as compared to the empty and the C-allele construct. NF-κB1 was identified to bind the C-allele rather than the G-allele, although the enhancer SNP (rs4936415) region was found to control transcription factor binding sites. Interaction of C-allele and NF-κB1 gene construct resulted in an increased enhancer activity. BD patients showed a significantly lower serum level of the IL-10Rα.ConclusionsThis study identified a single functional causal SNP, rs4936415, in the IL10RA super-enhancer, conferring BD susceptibility. The protective G-allele of non-coding rs4936415 located inside an enhancer region of IL10RA promoted the enhancer activity and increased the expression of IL10RA.The risk C-allele is able to specifically bind NF-κB1 and, in turn, promotes enhancer activity of IL10RA. This subsequently leads to an increased expression of IL10RA. Low expression of IL-10RA suggests a relative deficiency of NF-κB1 in BD.
| S-EPMC11750533 | biostudies-literature
Project description:Background: In Behçet's disease (BD), an auto-inflammatory vasculitis, an unbalanced gut microbiota can contribute to pro-inflammatory reactions. In separate studies, distinct pro- and anti-inflammatory bacteria associated with BD have been identified. Methods: To establish disease-associated determinants, we performed gut microbiome profiling in BD patients from the Netherlands (n = 19) and Italy (n = 13), matched healthy controls (HC) from the Netherlands (n = 17) and Italy (n = 15) and oral microbiome profiling in Dutch BD patients (n = 18) and HC (n = 15) by 16S rRNA gene sequencing. In addition, we used fecal IgA-SEQ analysis to identify specific IgA coated bacterial taxa in Dutch BD patients (n = 13) and HC (n = 8). Results: In BD stool samples alpha-diversity was conserved, whereas beta-diversity analysis showed no clustering based on disease, but a significant segregation by country of origin. Yet, a significant decrease of unclassified Barnesiellaceae and Lachnospira genera was associated with BD patients compared to HC. Subdivided by country, the Italian cohort displays a significant decrease of unclassified Barnesiellaceae and Lachnospira genera, in the Dutch cohort this decrease is only a trend. Increased IgA-coating of Bifidobacterium spp., Dorea spp. and Ruminococcus bromii species was found in stool from BD patients. Moreover, oral Dutch BD microbiome displayed increased abundance of Spirochaetaceae and Dethiosulfovibrionaceae families. Conclusions: BD patients show decreased fecal abundance of Barnesiellaceae and Lachnospira and increased oral abundance of Spirochaetaceae and Dethiosulfovibrionaceae. In addition, increased fecal IgA coating of Bifidobacterium, Ruminococcus bromii and Dorea may reflect retention of anti-inflammatory species and neutralization of pathosymbionts in BD, respectively. Additional studies are warranted to relate intestinal microbes with the significance of ethnicity, diet, medication and response with distinct pro- and inflammatory pathways in BD patients.
| S-EPMC7303268 | biostudies-literature
Project description:Systemic lupus erythematosus (SLE) has heterogeneous clinical manifestations. IFIH1 (interferon induced with helicase C domain 1) as one of antiviral helicase genes mediating type I interferon production, plays an essential role in the pathogenesis of SLE. The gene variants in IFIH1 could abnormally activate antiviral defenses and increased type I interferon signaling. The present study aimed to validate associations between single nucleotide polymorphisms (SNP) in IFIH1 and the pathogenesis of SLE. In total, rs1990760, rs3747517 and rs10930046 in IFIH1 are genotyped in 400 SLE patients and 659 health controls in Chinese cohort by an improved multiplex ligation detection reaction (iMLDR) technique. Significant associations were observed between alleles of IFIH1 (rs1990760 C > T, P = 0.005, OR = 1.36, 95%CI = 1.10-1.69; rs3747517 T > C, P = 0.004, OR = 1.31, 95%CI = 1.09-1.58, respectively) and SLE susceptibility. IFIH1 rs1990760 TT genotype carriers had lower serum levels of IL-18 (P < 0.001) and granzyme B (P < 0.001) than CC and CT genotype carriers. IFIH1 rs1990760 CT genotype carriers had higher anti-dsDNA-positive than CC and TT genotype carriers. In conclusion, IFIH1 polymorphisms (rs1990760 and rs3747517) were associated with SLE susceptibility and rs1990760 risk T allele related with IL-18 and granzyme B serum levels in SLE patients.
| S-EPMC6013496 | biostudies-literature
Project description:ObjectiveTo assess the proportion of postoperative complications of various surgeries in patients with Behçet's disease (BD) and compare the risk of surgical complications between BD patients and controls.MethodsWe analyzed 389 BD patients who underwent surgeries at Seoul National University Hospital between January 2003 and December 2019. Controls were 1:1 matched with BD patients based on age at surgery, sex, and type of surgery. Generalized estimating equation analyses were performed to compare the postoperative complications between BD patients and controls.ResultsAmong 632 surgeries in BD patients, 36 (5.7%) surgical site complications, including wound dehiscence (38.9%), bleeding (13.9%), infections (8.3%), anastomotic dehiscence (22.2%), and stricture (5.6%), occurred after median 12 days (IQR 7.8-22.0). Surgical site complications developed frequently after cardiac (33.3%) and vascular (22.2%) surgeries and rarely occurred after ophthalmic (1.5%) surgeries. Seventeen (2.7%) cases required reoperation within median 15 days (IQR 7.0-43.0). Four patients died within median 21 days (IQR 8.3-41.3 days). After adjustment for confounders, BD patients exhibited a significantly higher risk of surgical site complications (OR 3.4, 95% CI 1.4-8.0) and reoperation (OR 5.2, 95% CI 1.2-22.8) after cardiovascular surgery than controls. However, the risks of surgical site complications and reoperation after other types of surgery were similar in both groups.ConclusionsThe risk of postoperative complications varies according to the type of surgeries among BD patients. While cardiovascular surgeries result in higher perioperative complications in BD patients, ophthalmic surgeries show a safety profile similar to those in non-BD patients. Key Points • Patients with Behçet's disease exhibited an increased risk of surgical site complications and subsequent reoperations after cardiovascular surgery than controls. • The safety profile of ophthalmic surgery was comparable between patients with Behçet's disease and controls. • In patients with Behçet's disease, the risk of postoperative complications varies according to the type of surgery.
| S-EPMC11582265 | biostudies-literature
Project description:We aimed to evaluate the relationship of individual periodontal parameters with the severity of Behçet's disease (BD) and attempt to find the correlation between chronic periodontitis and BD. In this study, 74 registered subjects attending Behçet's clinic with BD symptoms were recruited. The diagnosis was based on the criteria presented by the international study group for BD (ISG) and the total clinical severity score was determined for each patient. All individuals underwent clinical examination to assess oral and periodontal status and presence of oral ulcers. Periodontal clinical parameters of bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) and also hygiene index (HI) and decayed, missing, and filled (DMF) teeth were noted and analyzed to assess the correlation with severity of BD. There was no significant correlation between DMF and severity of BD. The strong association was found between periodontal parameters (BOP, PD, and CAL) and the severity of BD (P < 0.001). It seems that relation of BD to oral health is higher up in severe forms of BD and periodontal diseases. Clinical association between the diseases might be due to a common underlying etiopathogenesis of periodontitis and BD.
| S-EPMC4789512 | biostudies-other
Project description:IntroductionThe objective was to investigate associations between the HLA-A gene and Behcet's disease (BD) and its clinical manifestations.MethodsGenotyping for the HLA-A locus was performed using the polymerase chain reaction-Luminex typing method in 223 BD patients and 1,398 healthy controls.ResultsThe phenotypic frequencies of HLA-A*02:07 (odds ratio (OR) = 2.03, P = 0.002), A*26:01 (OR = 1.85, P = 0.008), and A*30:04 (OR = 2.51, P = 0.006) tended to be higher in BD patients than in normal controls, but the frequency of A*33:03 (OR = 0.59, P = 0.003) tended to be lower in BD patients. A meta-analysis adopting our and the Japanese data confirmed the associations of HLA-A*02:07, A*26:01, and A*33:03 with BD. Furthermore, the frequencies of the HLA-A*02:07, A*26:01, and A*30:04 were significantly higher in patients with skin lesions (OR = 2.37, P < 0.0005, Pc < 0.012) and arthritis (OR = 2.32, P = 0.002, Pc = 0.048), with uveitis (OR = 3.01, P < 0.0005, Pc < 0.012), and with vascular lesions (OR = 9.80, P < 0.0005, Pc < 0.012) and a positive pathergy test (OR = 4.10, P = 0.002, Pc = 0.048), respectively, than in controls. In HLA-B*51 non-carriers, these associations were also significant, being much stronger between HLA-A*26:01 and uveitis (OR = 4.19, P < 0.0005, Pc < 0.012) and between HLA-A*30:04 and vascular lesions (OR = 13.97, P < 0.00005, Pc < 0.0012). In addition, HLA-A*30:04 was associated with genital ulcers in HLA-B*51 non-carriers (OR = 3.89, P = 0.002, Pc = 0.048).ConclusionsHLA-A*02:07, A*26:01, and A*30:04 were associated with increased risk for BD, while HLA-A*33:03 with decreased risk. HLA-A*02:07, A*26:01, and A*30:04 were associated with skin lesions and arthritis, with uveitis, and with vascular lesions, genital ulcers, and a positive pathergy test, respectively.
| S-EPMC3132038 | biostudies-literature