Interleukin-1 Receptor Antagonist Gene Polymorphism Research Articles

Interleukin (IL)-1B and IL-1 receptor antagonist gene polymorphisms in children with primary immune thrombocytopenia.

The pathophysiology and susceptibility of children to primary immune thrombocytopenia are linked to polymorphisms of the interleukin (IL)-1B and IL-1 receptor (IL-1R) antagonist genes. To investigated the association between the susceptibility and severity of primary ITP in children and the IL-1B and IL-1R antagonist gene polymorphisms. This comparative case-control study was con-ducted at the Menoufia University Hospital Hematology and Oncology Unit, Pediatric Department, between Au-gust 2022 and September 2023. The children were di vided into patients (28 boys, 22 girls) who received hospital and outpatient clinic care and controls (50 healthy age- and sex-matched children). The mutant homozygous GG genotype and mutant G allele of rs16944 of the IL1B gene were consi-derably greater in patients than in controls (P<0.001). Furthermore, the mutant homozygous II/II genotype and heterozygous I/II genotype of the IL-1R antagonist gene were considerably greater in the case versus control group. The mutant II allele was significantly more prevalent in patients versus controls (P<0.001). IL-1B and IL-1R antagonists may have a major impact on the development of immune thrombo-cytopenia. Furthermore, we found a relationship between IL-1B and IL-1R antagonist gene polymorphisms and the etiology of and children's.

Association between interleukin-1 receptor antagonist (IL-1RA) VNTR, gene polymorphism and breast cancer susceptibility in Iranian population:

Association between interleukin-1 receptor antagonist (IL-1RA) VNTR, gene polymorphism and breast cancer susceptibility in Iranian population:

Association of Interleukin-1 Receptor Antagonist ( IL-1RA ) Gene Polymorphism with Community-Acquired Pneumonia in North Indian Children: A Case-Control Study.

Background Community-acquired pneumonia (CAP) is the leading cause of death in children < 5 years of age. The primary objective of the study was to assess the association of IL-1RA gene polymorphism in children aged 2 to 59 months with CAP and the secondary objective was to assess the association of gene polymorphism with mortality among hospitalized CAP cases. Study Design This case-control study was conducted in a tertiary teaching institute in Northern India. Hospitalized children aged 2 to 59 months with World Health Organization-defined CAP were included as cases after parental consent. Age-matched healthy controls were recruited from the immunization clinic of the hospital. Genotyping was done using polymerase chain reaction to analyze the variable number of tandem repeats of IL-1RA gene polymorphism. Result From October 2019 to October 2021, 330 cases (123, 37.27% female), and 330 controls (151, 45.75% female) were recruited. Genotype A2/A2 of the IL-1RA gene was found to be associated with the increased risk for CAP children with adjusted odds ratio (AOR) of 12.24 (95% confidence interval [CI] 5.21-28.7, p < 0.001). A2 and A4 alleles were also found to be at risk for CAP. A1/A2 genotype was found to be protective for CAP with an AOR of 0.29 (95% CI 0.19-19.0.45). The genotype A2/A2 and A2 allele of IL-1RA gene was associated with child mortality with CAP cases. Conclusion In IL1RA gene, A2/A2 genotype and A2 allele were associated with increased risk of CAP and A1/A2 were found to be protective for CAP. The genotype A2/A2 and A2 was associated with CAP mortality.

Association between interleukin-1 receptor polymorphism and human herpesvirus 8 among lymphoma patients

Abstract Background: Human herpesvirus 8 (HHV-8) stimulates lymphoproliferation, by activating the signaling pathway of the interleukin-6 receptor, along with several other regulatory mechanisms. The presence of specific genetic variations governing immune responses can impact the promotion or suppression of malignant lymphoma. Polymorphisms in the gene cluster of interleukin-1 (IL-1) have been identified as significant contributors to the regulation of inflammation. Objective: This study aimed to determine the percentage HHV-8 and whether polymorphisms at IL-1 receptor antagonist (IL-1ra) locus modulate the risk of developing malignant lymphoma of a group of Iraqi patients in the Mid-Euphrates Sector, Iraq. Materials and Methods: A case-control study was conducted on 200 specimens obtained from patients with lymphoma and individuals without any apparent health conditions who served as the control group (considered normal individuals). The specimens were collected from various general hospitals and private clinics located in the Middle Euphrates region of Iraq. The study population included individuals aged between 17 and 75 years. Specimen collection took place between October 2022 and February 2023. Conventional polymerase chain reaction (PCR) was chosen for the detection of HHV-8 as well as IL-1ra gene polymorphism by sequencing. Results: According to PCR detection, 31 out of 64 (48.4%) of the specimens revealed PCR detection positivity for HHV-8, whereas 33 out of 64 (51.6%) specimens showed negative detection for HHV-8. The lymphoma which were most HHV-8-infected are related to the age stratum (56–75 years), accounted for 48%, whereas the age strata 15–35 years, and 36–55 years, each accounted for 23% and 29%, respectively. Conclusion: In view of the relatively small numbers included in our study, the present results indicate the possibility that HHV-8 and IL-1ra polymorphism may play a role in the tumor biology of lymphocyte and may contribute to their development.

Interleukin-1 Receptor Antagonist Gene Polymorphisms in Egyptian Children and Adolescents With Primary Immune Thrombocytopenia: Association With Disease Susceptibility, Response to Therapy, and Outcome.

Immune thrombocytopenia (ITP) is one of the most common hematologic disorders with poorly predictable clinical course and outcome. We studied the distribution of interleukin 1 receptor antagonist (IL-1Ra) gene polymorphism (intron-2) among children and adolescents with ITP and correlated IL-1Ra gene polymorphism to disease susceptibility, response to therapy, and outcome. Sixty children with ITP (mean age: 9.2±4.5y) and 100 healthy controls (mean age: 8.83±4.05y) were enrolled. The frequencies of the allele A2 and genotype A1A2 were significantly higher in patients compared with controls ( P <0.0001, P =0.0008, respectively). Allele A2 conferred 3.1 times increased relative risk for disease development. Allele A2 and genotypes A1A2 and A2A2 were significantly more frequent among remitted patients ( P =0.028 and 0.024, respectively). There was no significant difference between different genotypes and alleles regarding bleeding score ( P >0.05). Patients with polymorphic allele A2 (A1A2/A2A2) showed significantly better response to steroids than those with homozygous wild allele A1 ( P =0.028). IL-1Ra polymorphism might contribute to the susceptibility to ITP in Egyptian children. The presence of A2 polymorphic allele of IL-1Ra gene was found to be associated with better disease outcome and response to steroids than those with homozygous wild allele.

Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer

The aim of this study is to evaluate the association of interleukin-4 (IL-4) gene intron 3 and interleukin-1 receptor antagonist (IL-1Ra) gene intron 2 variable number tandem repeat (VNTR) polymorphisms with bladder cancer (BC) susceptibility in Turkish population. A total of 75 BC patients and 126 healthy controls were included in this case-control study. Genotyping for the interested polymorphisms were analyzed through polymerase chain reaction (PCR). The strength of association between both IL-4 and IL-1Ra gene VNTRs and BC susceptibility was estimated utilizing odds ratio (OR) with corresponding 95% confidence interval (CI). In the study, no statistically significant differences were determined in the allele distributions for either in IL-4 gene intron 3 VNTR (OR= 1.33; CI 0.704-2,41, p=0.390) or in IL-1Ra gene intron 2 VNTR polymorphisms (OR= 0.890; CI 0.569-1.394, p=0.346) between BC patients and control groups. The genotype distributions of IL-4 gene were estimated for RP1/RP2 (OR= 1.55; CI 0.11-7.74, p = 0.590) and RP1/RP1 (OR= 2.08; CI 0.48-9.06, p = 0.320), found no difference between BC and control groups. The genotype distributions of IL-1Ra gene were estimated for 2L (OR= 1.401; CI 0.753-2.610, p = 0.287) and 22 (OR=0.908; CI 0.252-3.276, p = 0.883) and found no difference between BC and control groups. This study suggest that there were no statistically significant differences determined either in genotype or allele distributions between BC patients and control groups for both IL-4 intron 3 VNTR and IL-1Ra intron 2 VNTR polymorphisms in Turkish population and therefore there was no association of these variants with BC risk in this population.

Association of Interleukin-1 Beta and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Plasma Levels with Diabetic Nephropathy.

Objective We investigated the relationships between interleukin- (IL-) 1β and IL-1 receptor antagonist (IL-1Ra) gene polymorphism and plasma levels in patients with diabetic nephropathy (DN). Methods The genotype and allele frequency distribution of IL-1β and IL-1Ra in 61 patients with DN and 48 healthy controls (HCs) were determined by kompetitive allele-specific PCR (KASP), and the plasma concentrations of IL-1β and IL-1Ra in DN patients and HCs were measured by enzyme-linked immunosorbent assays (ELISA). Results Significant differences were detected in the distribution of IL-1β (−511C/T) genotype and allele frequencies between the DN and HC groups (P < 0.05), with the T genotype being more frequent in DN patients than HCs (OR = 2.84, 95% CI: 1.489–5.416). The IL-1β (+3953C/T) and IL-1Ra (+8006C/T) genotypes and allele frequencies were not significantly different between the two groups (P > 0.05). The plasma IL-1β level was significantly higher (P < 0.01), while the plasma IL-1Ra concentration was significantly lower in the DN group than the HC group (P < 0.05). Furthermore, the plasma IL-1β level was significantly different between IL-1β (−511C/T) locus variants (P < 0.05). Conclusion The IL-1β (−511C/T) gene polymorphism was significantly associated with DN risk in the population of northern Guangxi, China, and the T allele maybe responsible for genetic susceptibility to DN.

COVID-19 Disease and Associated Thrombocytopenia: Pathogenesis and a Clue to the Etiology.

(1) Background: Hospital mortality in patients suffering from SARS-CoV-2 infection has been associated with thrombocytopenia. The present study was conducted to establish the correlation of thrombocytopenia and the severity of infection. The impact of IL-1Ra gene polymorphism on the incidence and severity of thrombocytopenia was also studied. (2) Methods: Various biochemical parameters measured in all the 1200 enrolled patients included full blood counts, renal and liver function tests, iron study, inflammatory markers, and coagulation assays. A further 70 patients each were selected from the severe thrombocytopenic and non-thrombocytopenic patient groups to study the IL-1Ra gene polymorphism by RCR. (3) Results: Out of 1200 patients, 436 (36.3%) had thrombocytopenia. Among these patients, 118 (27.1%), 75 (17.2%), and 42 (9.6%) had mild, moderate, severe, and very severe thrombocytopenia, respectively. Severe cases mostly resulted from peripheral consumption (73.5%), hemo-phagocytosis (15.4%), and bone marrow suppression (11.11%). A statistically significant correlation was found between the occurrence and severity of thrombocytopenia with perturbated levels of inflammatory markers and the presence of comorbidities. The IL-1Ra∗3 variant was found to be significantly associated with thrombocytopenia. The IL-1Ra∗2 variant was significantly seen among controls. (4) Conclusions: The present study revealed a significant correlation between thrombocytopenia and the severity of COVID-19 disease. Moreover, the IL-1Ra∗3 variant of IL-1Ra gene was associated with thrombocytopenia.

Interleukin-1 receptor antagonist gene polymorphisms in children with febrile convulsions

ObjectivesTo study the possible contribution of interleukin-1 receptor antagonist (IL-1Ra) gene polymorphisms to the susceptibility of febrile convulsions.BackgroundFebrile seizures (FSs) are considered the most common seizure disorder in childhood. They are considered a major cause of emergency department visits and a source of family anxiety. FSs of children involve an interaction between the immune-inflammatory process, cytokine activation, and genetic factors.Patients and methodsThis was a case–control study and included 55 children diagnosed to have febrile convulsions and 28 healthy children with no history of any type of convulsions or any neurological disorders. IL-1Ra gene polymorphisms were genotyped by PCR and compared in both groups.ResultsThe most common genotype for the IL-1Ra gene in both groups was I/I. The IL-1Ra I/I homozygote was significantly more frequent in patients with FSs than in healthy controls (76.4 vs. 46.3%, P = 0.01). In addition, IL-1Ra I/II genotype was significantly associated with resistance to FSs (P = 0.001). There were no significant differences between the studied groups regarding the distribution of other genotypes of IL-Ra gene. IL-1Ra allele I is associated with higher susceptibility to FSs among members of the case group (P = 0.03). However, IL-1Ra allele II is associated with resistance to FSs among the healthy control group (P = 0.01).ConclusionIL-1Ra I/I homozygous genotype is significantly associated with febrile convulsions.

Interleukin-1β and Interleukin-1 receptor antagonist gene polymorphism in pediatric patients with Helicobacter pylori-associated chronic gastritis.

The severity of Helicobacter pylori infection is determined by the interplay between bacterial virulence, host genetic and environmental factors. This study aimed to identify interleukin-1 beta (IL-1β) and interleukin receptor antagonist (IL-1RN) gene polymorphisms and their associations with H. pylori infection, and severity of chronic gastritis in Egyptian children. A case control study was conducted on 100 children (50 H. pylori positive and 50 controls). Genotyping of IL-1β-31 gene was done by PCR-CTPP (confronting two-pair primers), of IL-1β-511 was performed using allele specific PCR, and investigation of the variable number tandem repeat polymorphism of the IL-1RN gene was done by PCR. The genotype C/T of IL1β-511 was the predominant genotype (36/50; 72%) among H. pylori positive cases (p ≤ 0.001). The presence of C/T genotype at position 511 of IL1β was associated with increased risk of infection with H. pylori (p ≤ 0.001, odds ratio = 6.612) and with more severe disease (p = 0.004, odds ratio = 8.333). No association of IL-1β-31 or IL-1RN gene polymorphisms with H. pylori infection or with risk of severe gastric diseases was found. Children who carry two polymorphisms are almost four times at risk for development of H. pylori infection (p = 0.026, odds ratio = 3.937). Polymorphism at position -511 of IL1β gene is associated with increased risk of H. pylori infection as well as of severe corpus gastric disease in Egyptian children. This population should be considered a high-risk group, which needs regular gastric endoscopic surveillance, and should be target for H. pylori eradication. Lay summaryThe genotype C/T of IL1β-511 gene was the predominant genotype (36/50; 72%) among H. pylori positive children. Polymorphism at position -511 of IL1β gene is associated with increased risk of Helicobacter pylori infection as well as of severe corpus gastric disease in Egyptian children. No association of IL-1β-31 or IL-1RN gene polymorphisms with H. pylori infection or with risk of severe gastric diseases in Egyptian children.

Genetic polymorphism of interleukin-1 receptor antagonist in Type 1 diabetic children.

Interleukin-1 receptor antagonist (IL1RN) variable number tandem repeats (VNTRs) are not fully understood in Type 1 diabetes mellitus (T1DM). It may affect IL1RN level and modify the disease risk. We aimed to study IL1RN VNTR polymorphism in Egyptian children with T1DM to clarify its potential role as a risk factor for T1DM and its effect on plasma IL1RN level. A case-controlled study including 200 children (120 T1DM and 80 controls) was carried on. All children were subjected to genotyping of IL1RN VNTR. Plasma IL1RN was estimated by ELISA. The A1A2 and LS genotypes and A2 allele were significantly higher among cases compared to controls with increased T1DM risk (OR = 5.35, 2.56 and 3.13, respectively). The S allele was significantly elevated in cases compared to controls with 2.09-fold increased risk of having T1DM. The median plasma IL1RN significantly decreased in cases compared to controls. Within cases, IL1RN was significantly decreased in LS versus LL genotype. There is a strong relationship between IL1RN VNTR and T1DM in Egyptian children. A1A1 genotype, LL genotype, A1 allele, and L allele were protective. A1A2 and LS genotypes, short (S), and A2 alleles were risk factors. IL1RN was decreased in T1DM, especially in LS genotype. The relationship between IL1RN gene polymorphism and risk for T1DM among Egyptian children. Plasma IL1RN protein level in T1DM. Low IL1RN protein level in T1DM patients could be therapeutic targets for IL1RN medications in the future.

Impact of IL-1Ra Gene Polymorphism on the Etiology and Fate of Disease in Children with Immune Thrombocytopenic Purpura

Background. Immune thrombocytopenic purpura (ITP) is considered to be one of the common childhood autoimmune diseases, and the current study was initiated to study the effect of various factors, particularly interleukin 1 receptor antagonist (IL-1Ra) gene polymorphism, on the course of the disease. Methods. The current case-control study involved 60 newly diagnosed children presented with ITP (also included 60 age- and sex-matched healthy children). All enrolled individuals had complete blood count and molecular study to determine the polymorphic state of IL-1Ra gene using conventional polymerase chain reaction. Results. Sixty patients with ages 1-14 years and having a male/female ratio of 1 : 1.61 were enrolled in the current study. Forty-five children (75%) recovered within the first year, and 15 (25%) children developed chronic ITP. IL-1Ra ∗ 2 variant was found to be significantly associated with control groups ( P = 0.011 ), while IL-1Ra ∗ 3 was significantly associated with patients ( P = − 0.0163 ). Other factors having significant association with the remission rate include a previous history of immunization ( P &lt; 0.0001 ) and the symptoms at presentation ( P = 0.0009 ). Conclusions. The current study revealed a significant correlation of IL-1Ra gene polymorphism to the etiology and the course of the disease.

Polymorphisms of Encoding Genes IL1RN and P2RX7 in Apical Root Resorption in Patients after Orthodontic Treatment.

External apical root resorption (EARR) is one of the most serious complications associated with orthodontic treatment. The aim of the study was to analyze the relationships between selected single nucleotide polymorphisms (SNPs) in Interleukin 1 receptor antagonist (IL1RN), purinoreceptor P2X7 (P2RX7) and EARR in patients after orthodontic treatment. The study comprised 101 patients who underwent a complex orthodontic treatment with a combination of fixed appliances. Roots were measured based on orthopantomograms and lateral cephalometric radiographs taken before and at the end of the treatment using diagnostic software. Proportional measurements of selected teeth were made using the modified Linge and Linge methods. Based on the presence or absence of EARR, patients were divided into two groups: control group, 61 patients without EARR (with 0.90 ≤ rRCR ≤ 1.00), and EARR group, 40 patients with EARR (rRCR < 0.90). Root resorption in selected groups was also evaluated with the scores of Malmgren and Levander. SNP analysis was performed using the real-time polymerase chain reaction (PCR) method. The analysis indicated that a specific haplotype of P2RX7 (rs208294) and IL1RN (rs419598) modified the risk of EARR development (p < 0.05), with a Bonferroni correction. The analysis of the P2RX7 and IL1RN gene polymorphisms showed that the presence of SNPs of these genes may predispose individuals to EARR. These findings indicate that EARR is a complex condition influenced not only by environmental factors and needs further study on the genetic risk factors.

Association of Interleukin-1 and Inteleukin-1 Receptor Antagonist Gene Polymorphisms with Multiple Sclerosis in Azeri Population of Iran.

Cytokines as important mediators have a critical role in appropriate immune responses, the irregular production of which can lead to Multiple Sclerosis (MS). Proinflammatory cytokine interleukin-1 (IL-1) triggers inflammatory responses. Function and production of the cytokine are influenced by IL-1 coding gene polymorphism and those antagonists gene polymorphism. The aim of the present study was to evaluate the possible correlation between MS and IL-1 related alleles in Azeri population of Iran. Variable number tandem repeats (VNTR) genotypes of 150 MS patients and 220 healthy non-relative controls were determined. In the healthy controls, genotype TT at IL-1A (-889) location was significantly higher than the MS patients (p=0.0001). However, a significant difference was not found between the two groups in genotypic/allelic frequency at IL- 1B+ 3953 location. Evaluation of the IL-1RA gene revealed that genotype 1/2, and genotype 1/3 were significantly higher in the healthy controls and MS patients, respectively. Our findings indicated that the consumption of fast-food in MS patients was significantly higher than controls (p= <0.05). Also, a considerable number of MS patients had inappropriate dieting behaviors such as not eating breakfast (p= 0.0001), and irregular eating habits (p= 0.0001). Polymorphisms of the IL-1B genes and common alleles of IL-1RA were not considered as risk factors for MS disease. However, genotype TT at IL-1A (-889) location and the rare allele of IL-1RA3 can be a potential risk factor for the disease. Furthermore, inappropriate dieting behaviors and consumption of fast-food can increase the risk of MS.

Polymorphism of interleukin-1β and interleukin-1 receptor antagonist genes in children with autism spectrum disorders

In this study, we first investigated interleukin-1 beta (IL-1β) and IL-1 receptor antagonist (IL-1RA) levels in a cohort of Egyptian children with autism spectrum disorder (ASD) and in healthy controls. Second, we examined the single-nucleotide polymorphisms (SNPs) at positions −31 and − 511 of the IL-1β gene promoter and IL1RA and assessed the association between IL1B and IL1RA polymorphisms with ASD. We examined IL1β promoter polymorphism at −511 (IL-1β-511) and − 31 (IL-1β-31) and IL1RA gene polymorphism in 80 children with ASD and 60 healthy children. The children with ASD had significantly higher levels of IL-1β and IL-1RA than the controls. The children with ASD also had significantly higher frequencies of homozygous (CC) and heterozygous (TC) genotype variants of IL-1β-511, and IL-1RA than the controls. Moreover, the frequency of the IL-1β-511 allele (C) was higher in the ASD group than in the controls (p = .001). The homozygous and heterozygous variants of IL-1RA allele II were also significantly higher in the ASD group than in the control group. There was no significant association between the IL-1β-31 genotype and autism classes. However, there were significant differences in the distribution of the IL-1RA heterogeneous genotype and allele II among children with severe autism. The inflammatory role of cytokines has been implicated in a variety of neuropsychiatric pathologies, including autism. Our data show alterations in the IL-1β system, with abnormally increased serum levels of IL-1β and IL-1RA in the children with ASD. Further, polymorphisms in the IL-1β-511 and IL-1RA genotype variants correlated positively with autism severity and behavioral abnormalities. IL-1β-511 and IL-1RA gene polymorphisms could impact ASD risk and may be used as potential biomarkers of ASD. Variations in the IL-1β and IL-1RA systems may have a role in the pathophysiology of ASD.

Association between interleukin-1 beta gene, interleukin-1 receptor antagonist gene polymorphisms and urolithiasis: A literature review and meta-analysis

Several case-control studies have been performed in different populations to uncover the association between interleukin-1 beta gene, interleukin-1 receptor antagonist gene polymorphisms and urolithiasis. Here we decided to perform a literature review and meta-analysis to further estimate it. A systematic search was conducted in PubMed, Embase, Cochrane, clinicaltrials.gov, CNKI databases. To pool the effect size, odds ratios and 95% confidence intervals were used. Finally, five articles were included. Our results of literature review suggested that IL1RN IVS2 VNTR might be associated with the risk of urolithiasis. However, the results of meta-analysis suggested that IL-1beta -511C&gt;T, IL-1beta +3954C&gt;T, and IL1RN IVS2 VNTR might not be associated with the risk of urolithiasis. There were not enough data to fully confirm this association and the results should be interpreted with caution.

Interleukin 1 receptor antagonist (IL1RA) gene polymorphism and levels associated with adverse outcome in severe community-acquired pneumonia in children: A hospital-based study in India.

High morbidity and mortality due to community-acquired pneumonia (CAP) is seen in children under 5 years of age in India. Besides identified risk factors for CAP, there may be a phenotype-genotype association with cytokines, resulting in enhanced inflammatory response resulting in the adverse outcome (AO), namely complications and death. To assess the association of IL1RA gene polymorphism on serum levels of IL1RA and with AO in children under 5 years of age hospitalized with WHO-defined severe CAP. A prospective cohort study with nested case-control design conducted in a tertiary care teaching hospital after obtaining institutional ethical approval. Included were children between 2 and 59 months of age hospitalized with WHO-defined severe CAP with consistent radiological abnormalities. Excluded were those with suspected or proven cystic fibrosis, pulmonary tuberculosis, malignancy, immunodeficiency, and congenital heart disease. Polymerase chain reaction (PCR) was used to analyze the Variable Number of Tandem Repeats (VNTRs) of IL1RA gene polymorphism and ELISA test to detect serum levels of IL1RA. From 2014 to 2016, of 420 screened cases, 350 were eligible and included, of which 132 (37.7%) had no complication and 218 (62.3%) had AO, which included complications like empyema, pyopneumothorax, acute respiratory distress syndrome (ARDS), and septic shock of these 24 (6.9%) expired. Higher risk of AO was seen in A2A2 genotype (OR 11.18, p 0.0001) and lower in A1A1 genotype (OR 0.18, P < 0.0001). Serum IL1RA (ng/mL) was statistically significantly elevated in CAP with AO (2.55 ± 1.44) versus uncomplicated (0.87 ± 0.52) (P < 0.0001). In IL1RA gene, A1A1 genotype was associated with lower risk and A2A2 genotype with increased the risk of AO. Higher serum levels of IL1RA were found in A2A2 genotype indicating possibly enhanced inflammatory response resulting in AO of CAP.

Association of IL-1β, IL-1Ra and FABP1 gene polymorphisms with the metabolic features of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a highly prevalent endocrinopathy is currently being designated as chronic low grade inflammatory state. IL-1β, IL-1Ra and FABP1 are critical mediators of inflammatory processes and are speculated to play a role in the pathogenesis of PCOS. The aim of this study was to study the association of IL-β, IL-1Ra and FABP1 gene polymorphisms with PCOS and related metabolic features. 95 PCOS and 45 age matched healthy control subjects were enrolled in this study. Polymorphism in genes IL-1β, IL-1Ra and FABP1 was studied by PCR, PCR-RFLP and sequencing methods, respectively. Hormonal and lipid profiles were evaluated for all the subjects. Hormonal and lipid profiles showed significant differences between PCOS and control subjects. Allele and genotype frequencies of IL-1β, IL-1Ra and FABP1 gene polymorphisms did not vary between the control and PCOS group. However, T allele of C[-511]T variant of IL-1β, allele II in intron 2 of IL-1Ra and A allele of A/G variant of FABP1 (rs2197076) showed significant association with many metabolic features associated with PCOS. Polymorphism in genes encoding cytokines and proteins involved in lipid metabolism can provide insights into the genetics of the disease and may contribute to assess the associated risk of cardiovascular diseases (CVD), dyslipidemia and metabolic syndrome (MetS) associated with PCOS.

Interleukin-1B (IL-1B-31andIL-1B-511) and interleukin-1 receptor antagonist (IL-1Ra) gene polymorphisms in primary immune thrombocytopenia

BackgroundImmune thrombocytopenia (ITP) is an immune-mediated disease caused by autoantibodies against platelets membrane glycoproteins GPIIb/IIIa and GPIb/IX. The etiology of ITP remains unclear. This study evaluated the association of polymorphisms in interleukin (IL)-1B-31, IL-1B-511, and IL-1Ra with ITP.MethodsGenotyping of IL-1B-31, IL-1B-511, and IL-1Ra was performed in 118 ITP patients and 100 controls by polymerase chain reaction restriction fragment length polymorphism and detection of variable number tandem repeats.ResultsGenotype differences in IL-1B-31 and IL-1Ra were significantly associated with ITP. Patients showed a higher frequency of the IL-1B-31 variant allele (T) and a 1.52-fold greater risk of susceptibility to ITP (odds ratio [OR]=1.52, 95% confidence interval [CI]=1.04–2.22, P=0.034). The frequencies of both homozygous and heterozygous variant genotypes of IL-1B-31 were higher (OR=2.33, 95% CI=1.069–5.09, P=0.033 and OR=2.044, 95% CI=1.068–39, P=0.034) among patients and were significantly associated with ITP susceptibility. Both homozygous and heterozygous variant genotypes of IL-1Ra were also more frequent (OR=4.48, 95% CI=1.17–17.05, P=0.0230 and OR=1.80, 95% CI=1.03–3.14, P=0.0494) among patients and were associated with ITP risk. IL-1B-31 and IL-1Ra also showed significant association with severe ITP. However, IL-1B-511 was not associated with ITP.ConclusionIL-1B-31 and IL-1Ra polymorphisms may significantly impact ITP risk, and they could be associated with disease severity, which may contribute to the pathogenesis of ITP.

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation.

BackgroundAcute rejection (AR) after renal transplantation affects both patient and graft survival. There is growing evidence of the genetic association between cytokine or its receptor antagonist and AR in solid organ transplantation. The objectives of this study were to investigate the role of recipient TNF β, IL-10, IL-1β, and IL-1 receptor antagonist (ra) gene polymorphism, as well as traditional clinical variables such as panel-reactive antibody (PRA) levels, donor type, and HLA mismatches in AR following renal transplantation.Material/MethodsTNF β (+252A/G), IL-10 (−592A/C), IL-1β (−511C/T) and IL-1ra (86 bp VNTR) gene polymorphisms were determined in 195 renal allograft recipients with and without AR, using PCR. Both these genotypic variants and clinical risk factors were investigated for correlation with AR within the first year after renal transplantation.ResultsPatients with increased pre-transplant PRA levels (P<0.001) and donor type (P=0.012) were prone to the development of AR. After adjusting for all variables of P<0.2, a PRA level >10% (OR=4.515, 95% confidence intervals=1.738–11.727, P=0.002) and the receipt of a graft from a donation after cardiac death (DCD) donor (OR=2.437, 95% confidence intervals=1.047–5.673, P=0.039) remained significantly associated with AR in a multivariate logistic regression analysis. No correlation could be found between recipients with an episode and absence of acute rejection and the gene polymorphisms of these cytokines investigated in the present study.ConclusionsThis study shows that the presence of increased pre-transplant levels of PRA and the receipt of a graft from DCD donor other than cytokine gene polymorphisms are significant risk factors for AR in renal transplantation. To reduce the occurrence of AR, clinicians should take necessary measures to lower the PRA levels and pay more attention to patients who received a graft from a DCD donor.