Interleukin-1 Receptor Antagonist Polymorphisms Research Articles

The Prevalence of Thyrothyropin Receptor, Cytotoxic T Lymphocyte Antigen-4 and Interleukin-1 Receptor Antagonist Polymorphisms in The Group of Hashimoto Thyroiditis in Turkish Community and their Relationship with Clinical Parameters

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

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.

Interleukin-1 receptor antagonist (IL-1RA) and interleukin-4 (IL-4) variable number of tandem repeat polymorphisms in schizophrenia and bipolar disorder: an association study in Turkish population

BackgroundPro-inflammatory/anti-inflammatory cytokine imbalance in cerebrospinal fluid or plasma of schizophrenia (SCZ) and bipolar disorder (BD) patients has been documented over the last decade. We aim to examine the interleukin-1 receptor antagonist (IL-1RA) and IL-4 variable number of tandem repeat (VNTR) polymorphisms in SCZ and BD patients by comparing them with healthy controls.MethodsTwo hundred and thirty-four unrelated patients (127 patients with SCZ, 107 patients with BD) and 204 healthy controls were included. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis. In addition, the polymerase chain reaction technique was used to investigate IL-1RA and IL-4 VNTR polymorphisms.ResultsOur results showed that the distributions of IL-1RA and IL-4 genotype and the allele frequencies of SCZ or BD patients were not significantly different from the healthy control group. IL-1RA allele 2 homozygous genotype and IL-1RA allele 2 frequencies were non-significantly higher among SCZ patients than in controls.ConclusionsOur study indicates that the IL-1RA and IL-4 VNTR polymorphisms are not considered risk factors for developing SCZ and BD among Turkish patients.

Association between IL-1A, IL-1B and IL-1RN Polymorphisms and Peri-Implantitis: A Systematic Review and Meta-Analysis

Recent studies report that individuals with polymorphisms in the genes that encode for interleukin (IL)-1α and IL-1β (IL-1A and IL1B, respectively) and for IL-1 receptor antagonist (IL-1RN) may be more susceptible in developing peri-implantitis. Therefore, the current systematic review evaluates what is reported about the role of genetics, more specifically of single nucleotide polymorphisms (SNP) on IL-1 and variable number of tandem repeats (VNTR) on IL-1RN, in the development of peri-implantitis. This systematic review was carried out by screening PubMed, B-on, Cochrane and Scopus databases, for articles English, Spanish, and Portuguese, with no limit regarding the publication year. Eight articles were selected for systematic review and four for meta-analytic syntheses. Our results show that although there is a lack of consensus in the literature, there seems to be an association between IL-1A, IL-1B, and IL-1RN polymorphisms with peri-implantitis. The results of the meta-analysis showed that patients who have the polymorphic allele at position +3954 of the IL-1B gene have on average almost twice the risk of developing peri-implantitis (odds ratio = 1.986, 95% confidence interval).

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.

IL-1RN gene polymorphisms reduces thyroid cancer risk in Chinese Han population.

The purpose of this study was to investigate the effect of IL-1RN polymorphisms on thyroid cancer (TC) risk in Han population. Genotypes of four single nucleotide polymorphisms (SNPs) (rs17042888, rs928940, rs3181052, and rs452204) were analyzed by Agena MassARRAY. Meanwhile, we used the logistic regression to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), and significant differences were evaluated by t test and χ2 test. Findings found that allele "G" of rs452204 and rs3181052 in interleukin-1 receptor antagonist (IL-1RN) reduced the risk of TC. (OR = 0.72, 95% CI = 0.55-0.94, p = .017; OR = 0.73, 95% CI = 0.56-0.94, p = .017, respectively). Hierarchical analysis indicated that three SNPs (rs17042888, rs3181052, and rs452204) significantly reduced the risk of TC among females or individuals older than 48 years (p < .05). Our findings indicate that IL-1RN polymorphisms may contribute to a protective role against TC risk.

Genetic polymorphisms of IL1RN were associated with lumbar disk herniation risk in a Chinese Han population.

BackgroundInterleukin (IL)‐1 is a cytokine superfamily, which involved in the inflammatory process and immune response in human body. IL‐1 receptor antagonist (IL1RN) has been found to be associated with risk of lumbar disk herniation (LDH) in Finland samples. However, to date, there was no investigation focus on the polymorphisms of IL1RN in Chinese Han LDH patient.Materials and MethodsWe conducted a case–control study based on 498 LDH patients and 463 controls. Five single‐nucleotide polymorphisms (SNPs) in IL1RN were genotyped.ResultsAs a result, we found that the AG and GG genotypes of rs3181052 were associated with decreased risk LDH under the dominant model (OR = 0.74, 95%CI: 0.57–0.96, p = .025). In the stratification analysis, the frequency of the “A” allele of rs17042888 was significantly lower in elder LDH cases than in controls (OR = 0.723, 95%CI: 0.544–0.961, p = .025). In addition, the AG and AA genotypes of rs17042888 were associated with decreased risk of LDH in elder group under the dominant model (OR = 0.69, 95%CI: 0.49–0.98, p = .038). The GG genotype of rs315919 was identified have correlation with decreased risk of LDH in elder group under the recessive model (OR = 0.60, 95%CI: 0.37–0.97, p = .034).ConclusionsOur data showed that IL1RN may be a susceptibility gene for risk of LDH in Chinese Han population.

Gene-Environment Interaction between the IL1RN Variants and Childhood Environmental Tobacco Smoke Exposure in Asthma Risk.

(1) Background: Variants of the interleukin-1 receptor antagonist (IL1RN) gene, encoding an anti-inflammatory cytokine, are associated with asthma. Asthma is a chronic inflammatory disease of the airway influenced by interactions between genetic variants and environmental factors. We discovered a gene–environment interaction (GEI) of IL1RN polymorphisms with childhood environmental tobacco smoke (ETS) exposure on asthma susceptibility in an urban adult population. (2) Methods: DNA samples from the NYU/Bellevue Asthma Registry were genotyped for tag SNPs in IL1RN in asthma cases and unrelated healthy controls. Logistic regressions were used to study the GEI between IL1RN variants and childhood ETS exposures on asthma and early onset asthma, respectively, adjusting for population admixture and other covariates. (3) Results: Whereas the rare genotypes of IL1RN SNPs (e.g., GG in SNP rs2234678) were associated with decreased risk for asthma among those without ETS exposure (odds ratio OR = 0.215, p = 0.021), they are associated with increased risk for early onset asthma among those with childhood ETS (OR = 4.467, p = 0.021). (4) Conclusions: We identified a GEI between polymorphisms of IL1RN and childhood ETS exposure in asthma. Analysis of GEI indicated that childhood ETS exposure disrupted the protective effect of some haplotypes/genotypes of IL1RN for asthma and turned them into high-risk polymorphisms for early onset asthma.

Interleukin 1 receptor antagonist gene variable number of tandem repeats polymorphism and cutaneous melanoma.

Immunity and cytokines serve crucial roles in cutaneous melanoma. The present study investigated whether a variable number tandem repeat (VNTR) polymorphism of interleukin-1 receptor antagonist (IL-1RA) gene (IL-1RN) located in intron 2 (rs2234663) is associated with cutaneous melanoma. A total of 515 subjects were studied, 133 of which were cutaneous melanoma cases (72 stage I+II non-metastatic melanoma cases and 61 stage III+IV metastatic melanoma cases), and 382 subjects were matching healthy controls from the Friuli-Venezia-Giulia Region located in Northeast Italy, an area with a high melanoma incidence. The IL-1RN-VNTR polymorphism was determined by DNA fragment length analysis following PCR amplification. According to the number of 86-bp repeats, five different IL-1RN alleles were identified: Allele 1 (4-repeats), allele 2 (2-repeats, short allele), allele 3 (5-repeats), allele 4 (3-repeats) and allele 5 (6-repeats). Alleles with three or more 86-bp repeats, i.e. allele 1, 3, 4 and 5 were collectively denoted as long (L) repeats. The present study revealed that IL-1RN-VNTR 1/2 and 2/L genotypes were more frequent among patients with cutaneous melanoma (43.6 and 45.1%, respectively) compared with healthy controls [29.6 and 30.6%, respectively; odds ratio (OR), 1.84; CI, 1.22–2.77; P=0.003; and OR, 1.66; CI, 1.24–2.79; P=0.002, respectively]. Conversely, the IL-1RN-VNTR 1/1 genotype was less frequent among melanoma cases (45.9%) compared with healthy controls (57.9%; OR, 0.62; CI, 0.41–0.92; P=0.017). Comparison of metastatic vs. non-metastatic melanoma cases identified no significant differences. The present study first demonstrated that carriage of the 1/1 IL-1RN-VNTR genotype was protective, whereas 1/2 and 2/L was a risk factor for patients with cutaneous melanoma vs. healthy controls. The short allele 2 was associated with higher expression levels of IL-1RA, a potent competitive inhibitor of the proinflammatory cytokines IL-1α and IL-1β. VNTR-IL-1RN polymorphism may affect susceptibility to melanoma and, thus, it is a potential novel diagnostic biomarker for melanoma. The present study increased the understanding of genetic melanoma susceptibility/carcinogenesis, and may indicate novel strategies in the personalized prevention of cutaneous melanoma.

IL1RN Polymorphisms Are Associated with a Decreased Risk of Esophageal Cancer Susceptibility in a Chinese Population

Background: Recent evidence suggested that IL1RN (interleukin-1 receptor antagonist) polymorphisms increased the susceptibility to cancers. The present study aimed to evaluate whether IL1RN was related to esophageal cancer susceptibility in a Northwest Han Chinese population. Methods: The case-control study was conducted on 384 esophageal cancer patients and 499 healthy controls. We successfully genotyped four SNPs distributed in IL1RN. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to observe the expression of IL1RN in esophageal cancer tissues and normal tissues. RegulomeDB and HaploReg v4.1 were used to calculate possible functional effects of the polymorphisms. We also used genetic models to detect any potential association between IL1RN variants and esophageal cancer risk. Results: In our study, rs3181052 was associated with a reduced risk of esophageal cancer in the codominant (odds ratio [OR] = 0.70, 95% confidence interval [CI] 0.52–0.93, p = 0.040), the dominant (OR = 0.75, 95% CI 0.57–0.99, p = 0.041), and the overdominant (OR = 0.71, 95% CI 0.54–0.93, p = 0.012) model. The rs452204 was associated with a 0.76-fold (OR = 0.76, 95% CI 0.58–0.99; p = 0.043) decreased esophageal cancer risk under the overdominant model without adjustment. We also found that rs3181052 had a negative effect on esophageal cancer under the overdominant model (OR = 0.72, 95% CI 0.53–0.97, p = 0.033) adjusted for age and gender. In stratified analyses by age >55 years, rs3181052 reduced the risk of esophageal cancer in the dominant and overdominant models. In addition, rs315919 had a remarkable influence on esophageal cancer risk in females, while the association was not significant between rs3181052 and esophageal cancer risk in males. Conclusions: Our study provided the first evidence that IL1RN rs3181052, rs452204, and rs315919 are correlated with a decreased risk of esophageal cancer in a Northwest Han Chinese population. These findings may be useful for the development of early prognostics for esophageal cancer. However, further larger studies on different ethnic populations are warranted to verify these findings.

Positive correlation between interleukin-1 receptor antagonist gene 86bp VNTR polymorphism and colorectal cancer susceptibility: a case-control study.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Genetic variations in cytokine genes and their receptors lead to the severity of the disease. The interleukin-1 receptor antagonist (IL1RN) is a cytokine that inhibits interleukin-1 (IL-1) activity by binding to IL-1 receptors. Also, interleukin-4 (IL-4) is an anti-inflammatory cytokine that can play an important role in several cancers. The present case-control study was aimed to evaluate the association of IL-4 and IL1RN VNTR polymorphisms with the susceptibility to CRC in a sample of Iranian population provided by the Research Center for Gastroenterology and Liver Disease at Taleghani Hospital, Tehran. A total of 123 patients diagnosed with CRC and 152 healthy controls were recruited in the present study. Genomic DNA was extracted by salting out method from whole blood and genotyping of IL1RN and IL-4 VNTR polymorphisms were determined by PCR-based technology. Our study manifested the frequency of 1/2 and 2/4 genotypes of IL1RN 68bp VNTR polymorphism are significantly different between both groups (p = 0.0001 and p = 0.01 respectively). However, we could not find any correlation between IL-4 VNTR polymorphism and CRC cancer. It seems that 1/2 and 2/4 genotypes of IL1RN are correlated with CRC susceptibility in our population, although, more studies are needed to confirm our results.

Lack of association between interleukin-1 receptor antagonist gene 86-bp VNTR polymorphism and ischemic stroke: A meta-analysis.

The results of published studies which examined the association between variable number tandem repeat (VNTR) polymorphism of interleukin-1 receptor antagonist (IL-1RN) and ischemic stroke (IS) are conflicting. Thus, we performed a meta-analysis to examine the potential association between IL-1RN VNTR polymorphism and IS risk. A systematic literature search of PubMed, Embase, Medline, Web of Science, Cochrane Library, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, CQVIP, and WANFANG Database identified 10 studies with 2331 cases and 3335 controls. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to evaluate the strength of the association. Subgroup analysis and meta-regression analysis were used to investigate the potential sources of heterogeneity. Begg funnel plots were used to explore the publication bias. In this study, no enough proof was found to prove the association between IL-1RN 86-bp VNTR polymorphism and IS risk with random-effects model in the homozygous model (1/1 vs 2/2, OR = 0.97, 95% CI = 0.50-1.87, Pheterogeneity = .00), the heterozygous model (1/2 vs 2/2, OR = 0.64, 95% CI = 0.41-1.01, Pheterogeneity = .10), the dominant model (1/1 + 1/2 vs 2/2, OR = 0.85, 95% CI = 0.51-1.42, Pheterogeneity = .02), the recessive model (1/1 vs 1/2 + 2/2, OR = 0.69, 95% CI = 0.46-1.03, Pheterogeneity = .00), and allelic model (1 vs 2, OR = 1.24, 95% CI = 0.89-1.74, Pheterogeneity = .00). A marginally significant negative association was observed between IL-1RN 86-bp VNTR polymorphism and IS risk in the heterozygous model in the fixed-effects model (1/2 vs 2/2, OR = 0.71, 95% CI = 0.53-0.95, Pheterogeneity = .10). In subgroup analyses, similar association was found in the group whose control size was lower than 300. In conclusion, our results suggested that there was no sufficient evidence to support the association between IL-1RN 86-bp VNTR polymorphism and IS. Further large epidemiologic studies need to be done to confirm these findings.

Association between IL-1RN VNTR polymorphism and head and neck cancer in Indonesian population

The interleukin-1 receptor antagonist (IL-1RN) is a natural antagonist of IL-1 receptors, and its 86-bp variable number tandem repeat (VNTR) polymorphism within intron 2 has been associated with the development of several cancers. This study aimed to evaluate the IL-1RN polymorphism for its potential association with head and neck cancer in Indonesia population. Polymerase chain reaction analysis was performed on stored blood-derived DNA samples from 110 control participants and 90 patients with head and neck cancer for the IL-1RN VNTR polymorphism. Chi-square and odds ratio were used for the statistical analysis. This study showed no significant difference in the frequencies of genotypes or alleles in either the control or the cancer groups. However, a larger sample size could reveal a more significant difference between the groups. The IL-1RN VNTR polymorphism was not associated with head and neck cancer in the studied Indonesian population.

The Allele 2 of the VNTR Polymorphism in the Gene That Encodes a Natural Inhibitor of IL-1β, IL-1RA Is Favorably Associated With Chronic Otitis Media.

Objectives Chronic otitis media (COM) is followed by irreversible tissue damage and destruction of the middle ear structures, with the possibility of complications under the maintenance of inflammation. Inflammatory mediators such as cytokines play a crucial role in the initial stage of inflammation. The aim of this study was to evaluate the association of the polymorphisms in two innate immunity/inflammation cascade genes from interleukin-1 (IL-1) gene cluster with COM with regard to cholesteatoma.Methods In the cross-sectional case-control study, DNA samples were collected from 189 patients with COM and 119 controls from a population of Serbia. The +3953 C/T (rs1143634), TaqI polymorphism in interleukin-1 beta (IL-1β) gene and 86 bp variable number tandem repeat (VNTR, rs2234663) polymorphism in the IL-1 receptor antagonist (IL-1RA) gene were analyzed by polymerase chain reaction.Results The IL-1β TaqI polymorphism was not significantly different in patients compared with the control group. The significant difference between patients and controls was observed for both, genotype and allele frequencies of IL-1RA VNTR polymorphism (chi-square P<0.01). We found that carriers of IL-1RA allele 2 (odds ratio, 0.47; 95% confidence interval, 0.29 to 0.76; P=0.004) have a favorable association with COM, using multivariate logistic analysis that included both polymorphisms, age and sex. The IL-1RA allele frequency distribution was significantly different with regard to cholesteatoma.Conclusion The carriers of allele 2 of VNTR IL-1RA polymorphism had a decreased odds ratio for COM, which is in agreement with findings in other inflammatory disease and its previous association with higher IL-1RA levels. Possible down-regulation of IL-1 mediated proinflammatory signaling pathways via IL-1RA in COM as well as results of our study should be further investigated and replicated.

Association of of IL-1 receptor antagonist (IL-1RN) and interleukin-1β genes (IL-1β) polymorphisms with recurrent pregnancy loss in Iranian Azeri women.

Objective One of the most important problems in human reproduction is recurrent pregnancy loss (RPL). RPL is defined as three or more consecutive abortions in the first trimester of pregnancy. The association between the polymorphisms in the immunological factors and RPL was investigated. The aim of our study was to determine the association of interleukin receptor antagonist (IL-IRN) and interleukin-1β (IL-1β) polymorphisms with RPL in Iranian Azeri women. Materials and methods The study participants consisted of 100 women with RPL of Iranian Azeri origin. The control group comprised 100 age- and ethnically-matched healthy women of the same reproductive age. Genomic DNA was extracted from the whole blood and genotype determinations were performed using polymerase chain reaction (PCR) amplification followed by restriction fragment length polymorphism (RFLP) analysis. Results Our results showed no significant relationship between IL-1RN polymorphism and RPL. The homozygous state in -857 C/T variant was seen to be higher in RPL patients than in control subjects. Also frequency of wild type genotype was lower in RPL patients than in controls. However, this associations was not significant. Conclusion This study suggested that -511 C/T (rs16944) and -31 C/T (rs1143627) polymorphisms in IL-1β gene may not be involved in RPL in Iranian Azeri women. Also the promoter polymorphism of the IL-1RN gene may not play a role in the susceptibility to RPL.

Divisive influence of interleukin-1 receptor antagonist polymorphisms in melanoma patients.

The interleukin-1 receptor antagonist (IL-1RA) contributes to tumor survival and progression in multiple cancer entities. IL-1RA polymorphisms influence IL-1RA expression patterns and function. A known polymorphism was correlated with clinical outcomes in melanoma patients with particularly aggressive disease. DNA of 343 controls and 97 melanoma patients with poor prognostic indicators (time from diagnosis to death, nodal status, metastasis) was analyzed for a variable number of tandem repeat polymorphisms (VNTR) of the IL-1RA gene. Five alleles containing two (allele 2), three (allele 4), four (allele 1), five (allele 3) or six (allele 5) 86-bp repeats were targeted via PCR amplification. Genotype 1/2 is less common in the melanoma patient group vs. the control (28.8% vs. 39.6%; p = 0.06). Significant was the stage of the melanoma in order to predict the survivability (p = 0.008). The 1/1 and 1/2 genotype appeared to have lower hazards ratios than the 2/2 genotype (p > 0.05). Compared to the general population, the distribution of alleles coding for IL-1RA is different in melanoma patients. This alteration and the potential impact on tumor protein function and systemic inflammatory response may warrant further investigation.

Association of a genetic polymorphism of IL1RN with risk of acute pancreatitis in a Korean ethnic group.

Background/AimsSeveral epidemiological studies have validated the association of interleukin gene polymorphisms with acute pancreatitis (AP) in different populations. However, there have been few studies in Asian ethnic groups. We aimed to investigate the relationships between inflammatory cytokine polymorphisms and AP as pilot research in a Korean ethnic group.MethodsPatients who had been diagnosed with AP were prospectively enrolled. DNA was extracted from whole blood, and DNA sequencing was subsequently performed. Single-nucleotide polymorphisms (SNPs) of the interleukin 1β (IL1B), interleukin 1 receptor antagonist (IL1RN), and tumor necrosis factor α (TNFA) genes of patients with AP were compared to those of normal controls.ResultsBetween January 2011 and January 2013, a total of 65 subjects were enrolled (40 patients with AP vs. 25 healthy controls). One intronic SNP (IL1RN −1129T>C, rs4251961) was significantly associated with the risk of AP (odds ratio, 0.304; 95% confidence interval, 0.095 to 0.967; p = 0.043). However, in our study, AP was not found to be associated with polymorphisms in the promoter regions of inflammatory cytokine genes, including IL1B (−118C>T, c47+242C>T, +3954C/T, and −598T>C) and TNFA (−1211T>C, −1043C>A, −1037C>T, −488G>A, and −418G>A).ConclusionsIL1RN −1129T>C (rs4251961) genotypes might be associated with a significant increase of AP risk in a Korean ethnic group.

IL-1RN gene polymorphisms are associated with breast cancer risk in a Chinese Han population.

The interleukins (ILs) are a large family of endogenous cytokines that are crucial in the regulation of inflammation and immunological responses. The IL-1 receptor antagonist (IL-1RN) has been found to be associated with risk breast cancer (BC) in Korean and Indian women. However, little information is found about the polymorphisms of IL-1RN in Chinese Han BC patients. We investigated the association between single-nucleotide polymorphisms (SNPs) in IL-1RN and BC risk in a case-control study that included 530BC cases and 628 healthy controls. Six tag SNPs in IL-1RN were selected and genotyped using the Sequenom MassARRAY platform (Sequenom, San Diego, CA, USA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and sex. In the allele model, we found that the frequency of the 'T' allele of rs928940 was significantly lower in BC cases than in controls (OR=0.776, 95% CI=0.611-0.985, p=0.037). In the genetic model analysis, five susceptibility SNPs were found to be associated with BC risk: the minor allele 'G' of rs315919, rs3181052 and rs452204 were associated with a decreased risk of BC under dominant model (p<0.05), whereas the minor alleles 'T' and 'C' of rs928940 and rs4252019 were associated with a decreased risk of BC under both the codominant and dominant models (p<0.05), which suggested these SNPs may play a protective role against BC risk. The haplotype 'TAGC' constructed by rs928940, rs3181052, rs452204 and rs4252019 was associated with a decreased risk of BC (OR=0.33; 95% CI=0.12-0.94; p=0.038). The data obtained in the present study shed new light on the association between genetic polymorphisms of IL-1RN and BC susceptibility in the Chinese Han population.

The effects of tumor necrosis factor-α (TNF-α) and IL-1 receptor antagonist (IL-1Ra) polymorphisms on recurrent abortion in Azari women.

Recurrent pregnancy loss (RPL) is a heterogeneous condition consisting of three or more consecutive abortions before the 20 weeks of gestation. The tumor necrosis factor alpha (TNF-α) gene plays a crucial role in immunology and inflammation responses. Interleukin 1 receptor antagonist (IL-1RN) is an important anti-inflammatory molecule which plays important roles in pregnancy. The aim of this study was to investigate effects of TNF-α and IL-1Ra polymorphisms on RPL in Azari women. The study participants consisted of 100 women with RPL from Iranian Azeri Turkish origin. The control group comprised 100 age and ethnically matched healthy women in the reproductive age. Genomic DNA was extracted from the whole blood and genotype determinations were performed using PCR amplification followed by restriction fragment length polymorphism (RFLP) analysis. No significant association was indicated between IL-1Ra and RPL among Iranian Azeri Turkish women. Unlike the homozygous state, significantly higher frequency of -857 C/T variant was seen in RPL patients than control subjects. Significantly lower frequency of wild type genotype was observed in RPL patients than of controls. Any association was found between the other TNF-α polymorphisms and RPL. TNF-α -857 C/C variant might represent protective effect against RPL and the -857 C/T variant might be a genetic risk factor for the occurrence of RPL. Invariant differences in the prevalence of -511 C/T and -31 C/T polymorphisms and IL-1RN VNTR between RPL patients.

Candidate gene analysis in pathogenesis of surgically and non-surgically treated necrotizing enterocolitis in preterm infants

Necrotizing enterocolitis (NEC) is one of the most severe and unpredictable complications of prematurity. There are two possible mechanisms involved in the pathogenesis of NEC: individual inflammatory response and impaired blood flow in mesenteric vessels with secondary ischemia of the intestine. The aim of this study was to evaluate the possible relationship between polymorphisms: Il-1β 3953C>T, Il-6 −174G>C and −596G>A, TNFα −308G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il-1RN VNTR 86 bp) and three polymorphisms that may participate in arteries tension regulation and in consequence in intestine blood flow impairment: eNOS (894G>T and −786T>C) and END-1 (5665G>T) and NEC in 100 infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. In study population, 22 (22%) newborns developed NEC. Surgery-requiring NEC was present in 7 children. Statistical analysis showed 20-fold higher prevalence of NEC in infants with the genotype TT [OR 20 (3.71–208.7); p = 0.0004] of eNOS 894G>T gene polymorphism. There was a higher prevalence of allele C carriers of eNOS 786T>C in patients with surgery-requiring NEC [OR 4.881 (1.33–21.99); p = 0.013]. Our investigation did not confirm any significant prevalence for NEC development in another studied genotypes/alleles. This study confirms the significant role of polymorphisms that play role in intestine blood flow. Identifying gene variants that increase the risk for NEC development may be useful in screening infants with inherent vulnerability and creating strategies for individualized care.