Receptor Antagonist Gene Polymorphism Research Articles

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.

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 between interleukin-1 receptor antagonist (IL-1ra) VNTR, gene polymorphism and breast cancer susceptibility in Iranian population: Experimental and web-based analysis.

Breast cancer is one of the leading causes of cancer mortality. Growing evidence indicates that interleukins and its polymorphisms are involved in the pathogenesis of breast cancer. Variable number of tandem repeat (VNTR) polymorphism can affect transcription rate, mRNA stability and also the resulting protein expression and activity. Hence, present study aimed to assess the possible association between interleukin-1 receptor antagonist (IL-1Ra) VNTR polymorphism, and breast cancer susceptibility in Iranian population. A total of 300 Iranian individuals, 150 breast cancer patients and 150 age-matched healthy women, were included in this study. DNA extracted by salting out method and genotyping was done using the polymerase chain reaction. The frequency of the allele 2(5% vs. 22%) and the 2/2 genotype (22% vs. 46%) of IL-1Ra VNTR polymorphism was significantly higher in healthy control compared to breast cancer patient: therefore, A2 allele may play a protective role against breast cancer and its progression (p = .0001 and OR = 0.105, 95% CI: [0.044-0.248]). The allele 2 and 2/2 genotype of the IL-Ra VNTR polymorphism can be a protective factor against breast cancer susceptibility.

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.

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.

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.

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.

Should COVID-19 take advice from rheumatologists?

Should COVID-19 take advice from rheumatologists?

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.

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.

Interleukin-1 receptor antagonist gene polymorphism and obesity a pilot study from Egypt.

The main adverse consequences of excess bodyweight are cardiovascular disease, type II diabetes, and several cancers. IL-1Ra serum concentration has been reported earlier to increase in human obesity and it is therefore assumed that the polymorphism of IL-1Ra may influence cytokine production. The study was designed to investigate whether the IL-1Ra polymorphism was associated with obesity. A total number of 66 individuals; 20 normal (BMI <25 Kg/m2), 20 overweight (BMI 25-29.9 Kg/m2) and 26 obese (BMI More than 30.0 Kg/m2) were enrolled in this study. Genotyping was performed using a polymerase chain reaction PCR amplification of the intron-2 fragment harboring a variable number of tandem repeat (VNTR) nucleotide sequences 86 bp of tandem repeat. The PCR products were separated on 2% agarose gel. Statistical analysis was performed using SPSS software (version 11.5). The genotype and allelic frequencies showed a significantly difference between normal vs. overweight and normal vs. obese (p-values: 0.001; 0.0001; 0.0018 and 0.001 respectively). Although, The presence of Allelic frequencies for Allele I between normal vs. overweight and normal vs. obese showed > 2 folds risk in overweight and >3 folds in obese (OR=2.3; 95% CI=0.796-8.620 & OR=2.1; 95% CI=0.972-10.265 respectively). Allele II between normal vs. overweight and normal vs. obese showed > 3.5 folds risk in overweight and >1.5 folds in obese (OR=3.45; 95% CI=0.836-9.210 & OR=1.63; 95% CI=0.892-9.11 respectively) and Allele V between normal vs. overweight and normal vs. obese showed > 2 folds risk in overweight and >1.5 folds in obese (OR=1.99; 95% CI=0.821-9.10 & OR=1.95; 95% CI=0.882-8.975 respectively).This may suggest that IL-1Ra appears to be induced by inflammatory stimuli as well as obesity-associated factors. This is relatively a pilot study; but nevertheless, may assist in identifying the pathophysiological cause for obesity

Interleukin-1 receptor antagonist gene polymorphism, adverse pregnancy outcome and periodontitis in Turkish women

ObjectiveThe aim of this study was to determine associations between interleukin (IL)-1A (+4845), IL-1B (+3954), and IL-1 receptor antagonist (RN) variable number tandem repeat polymorphisms and adverse pregnancy outcomes and periodontitis in a Turkish women. DesignA total of 156 patients, including 64 women with normal birth outcome (NB) and 92 women with preterm/low birth weight outcome (PLBW) were included in this case-control study. Within 24h after labor, maternal demographic characteristics and clinical periodontal parameters were recorded. The distribution and genotype frequencies of IL-1 were analyzed with polymerase chain reaction-restriction fragment length polymorphism assay. Statistical analyses were carried out for clinical periodontal parameters, genotype frequencies, and to identify explanatory variables for PLBW. ResultsPLBW was associated with maternal age (p<0.05), irregular prenatal care (p<0.001), previous PLBW (p<0.05), and antibiotic use during pregnancy (p<0.05). Measurements of probing depth and clinical attachment level (CAL) were significantly higher in the PLBW group than in the NB group (p<0.001). PLBW was associated with IL-1RN allele 2 (p<0.001). Moreover, stepwise logistic regression analysis showed that CAL (OR 1.39, 95% CI: 1.04–1.85) and IL-1RN polymorphism (OR 7.92, 95% CI: 2.76–22.79), previous PLBW (OR 5.01, 95% CI: 1.08–23.17), age (OR 1.22, 95% CI: 1.04–1.44) were predictors found to increase the risk of PLBW (p<0.05). There was a negative association between PLBW and regular prenatal care, total number of births, use an antibiotic during pregnancy period (p<0.05). ConclusionOur study showed that, IL-1RN allele 2, periodontal disease characterized with clinical attachment loss, previous PLBW and age could be an important risk factors for PLBW.

Meta-analysis of associations of IL1 receptor antagonist and estrogen receptor gene polymorphisms with systemic lupus erythematosus susceptibility.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects a number of different organs and tissues. Interleukin-1 (IL1) and estrogen are considered potential elements in the pathology of SLE. Recently, the variable number of tandem repeats (VNTR) polymorphism in the IL1 receptor antagonist gene (IL1-RN) and PvuII (rs2234693) and XbaI (rs9340799) polymorphisms in the estrogen receptor 1 gene (ESR1) have been associated with a predisposition to SLE. However, the evidence for these associations is inconclusive. We therefore conducted a meta-analysis to validate the roles of these polymorphisms in SLE susceptibility. We searched four databases and identified a total of 17 eligible articles comprising 24 studies. The Newcastle-Ottawa quality assessment scale was used to assess the qualities of the selected studies. We assessed the strengths of the associations using odds ratios (ORs) with 95% confidence intervals (95% CIs). Regarding the IL-1RN VNTR, the 2 allele significantly increased SLE susceptibility (2 vs. L: OR = 1.34, 95% CI = 1.03–1.73, P = 0.03). The ESR1 PvuII CC/CT genotype was also associated with SLE susceptibility (CC/CT vs. TT: OR = 1.25, 95% CI = 1.06–1.47, P = 0.01), and the difference was especially pronounced among Asians (CC/CT vs. TT: OR = 1.33, 95% CI = 1.04–1.69, P = 0.02). No significant association between the ESR1 XbaI polymorphism and SLE susceptibility was observed in the overall analysis. However, a marginally significant association between the GG/GA genotype was found in individuals of Asian descent (GG/GA vs. AA: OR = 1.30, 95% CI = 1.01–1.67, P = 0.04). These results indicate that the IL1-RN VNTR 2 allele, ESR1 PvuII CC/CT genotype and ESR1 XbaI GG/GA genotype may increase SLE susceptibility, especially in Asian individuals.

Interleukin 1β and interleukin 1 receptor antagonist gene polymorphisms and cervical cancer: a meta-analysis.

Previous studies investigating the association between interleukin 1β (IL-1β) and its receptor antagonist (IL-1RN) polymorphism and cervical cancer risk have reported controversial results. Thus, we examined these associations by performing meta-analyses. Fourteen studies testing the association between IL-1β and/or IL-1RN gene polymorphisms and cervical cancer were examined: 5 studies of IL-1β-511C/T, 3 studies of IL-1β-31T/C, and 6 studies of IL-1RN. Overall and ethnicity-specific summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for cervical cancer associated with these polymorphisms were estimated using fixed- and random-effects models. Heterogeneity and publication bias were evaluated. Meta-analysis of all 6 studies showed variant genotypes of IL-1RN to be associated with an elevated cervical cancer risk (RN2/RN2 vs RN1/RN1: OR, 2.64; 95% CI, 1.29-5.40; recessive: OR, 2.15; 95% CI, 1.06-4.38; dominant: OR, 1.60; 95% CI, 1.07-2.38). Combined analysis indicated that IL-1β-511C/T polymorphism was also associated with increased risk of cervical cancer (TT vs CC: OR, 1.56; 95% CI, 1.22-1.99; CT vs CC: OR, 1.61; 95% CI, 1.31-1.99; dominant: OR, 1.60; 95% CI, 1.31-1.95). No significant association of IL-1β-31T/C and cervical cancer risk was detected. There was no evidence of publication bias. This meta-analysis suggested that the IL-1RN and IL-1β-511C/T polymorphisms may contribute to genetic susceptibility of cervical cancer. More studies are needed to further evaluate the role of the IL-1β-31T/C polymorphism in the etiology of cancer.

Association of interleukin 1 receptor antagonist (IL1RN) gene polymorphism with recurrent pregnancy loss risk in the North Indian Population and a meta-analysis.

An appropriate ratio of interleukin 1 beta to interleukin 1 receptor antagonist (IL1Ra) is required for successful pregnancy. Our objective was to study the genetic association between IL1RN variable numbers of tandem repeat (VNTR) polymorphism and recurrent pregnancy loss (RPL). To analyze the association between IL1RN VNTR allele and RPL, we investigated the IL1RN VNTR polymorphism in 136 RPL patients and in 200 healthy control women. Meta-analysis on this polymorphism was conducted to support our findings. PCR based approach was used to analyze IL1RN VNTR polymorphism and it was further confirmed by sequencing. Systematic review and meta-analysis was done using electronic database (Pub-Med, Google Scholar and Ovid) up to February 27, 2013. This meta-analysis was assessed by comprehensive meta-analysis software version 2. For meta-analysis 549 cases and 1,450 controls were included. The frequency of IL1RN genotype 2/2 was significantly higher in RPL compared to control group (AORs 3.10, 95 % CI 1.58-6.11, p = 0.001). The presence of rare allele also increased the risk of RPL significantly (ORs 1.63, 95 % CI 1.16-2.29, p = 0.004). The meta-analysis stratified by ethnicity showed that individuals with allele 2 had increased risk of RPL (OR 1.29, 95 % CI 1.04-1.61, p = 0.01), in Asians population by using fixed model. However the data of the present study clearly suggests that IL1RN VNTR polymorphism is a genetic risk factor for pregnancy loss in the study population.

Gene polymorphisms and febrile neutropenia in acute leukemia--no association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 are associated with the disease in Turkish patients: a preliminary study.

The aim of this study was to investigate the mannose-binding lectin 2 (MBL-2), interleukin (IL)-4, Toll-like receptor 4 (TLR-4), angiotensin converting enzyme (ACE), chemokine receptor 5 (CCR-5), and IL-1 receptor antagonist (RA) gene polymorphisms (GPs) in acute leukemias (ALs) and to evaluate their roles in febrile neutropenia (FN) resulting from chemotherapy. The study included 60 AL patients hospitalized between the period of July 2001 and August 2006. Polymorphisms for the genes ACE(I/D), CCR-5, IL-1RA, MBL-2, TLR-4, and IL-4 were typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymerase. Genotype frequencies for these genes were compared in the patient and control groups. The relationships between the genotypes and the body distribution of infections, pathogens, the duration of neutropenia, and febrile episodes in AL patients were evaluated. No significant differences in either the genotype distribution or the allelic frequencies of TLR-4, IL-4, CCR-5, IL-1RN GPs were observed between patients and healthy controls. The AB/BB genotype (53.3%) in the MBL-2 gene was found to be significantly higher in the AL patients compared with control groups. There were correlations between the presence of MBL-2, TLR-4, and ACE polymorphisms and clinical parameters due to FN. Overall, bacteremia was more common in MBL BB and ACE DD. Gram-positive bacteremia was more common in ACE for ID versus DD genotype. Gram-negative bacteremia was more common for both the MBL-2 AB/BB genotype and TLR-4 AG genotype. Median durations of febrile episodes were significantly shorter in ACE DD and MBL AB/BB. Although TLR-4, ACE, and MBL-2 GPs have been extensively investigated in different clinical pictures, this is the first study to evaluate the role of these polymorphisms in the genetic etiopathogenesis of FN in patients with ALs. As a conclusion, TLR-4, ACE, and MBL-2 genes might play roles in the genetic etiopathogenesis of FN in patients with ALs.