Interleukin-1 Gene Cluster Polymorphisms Research Articles

Association of Interleukin-1 Gene cluster polymorphisms with coronary slow flow phenomenon.

Objective:Coronary slow flow phenomenon (CSFP) is characterized by the decreased rate of contrast progression in epicardial coronary arte-ries in the absence of significant coronary stenosis. Mounting evidence has showed a significant association between inflammation and CSFP severity. This study aimed to evaluate possible associations between interleukin-1 receptor antagonist (IL-1ra) gene variable number tandem repeat (VNTR), IL-1β -511 single nucleotide (SNP), and IL-1β+3954 SNP mutations with CSFP.Methods:Forty-eight patients with CSFP and 62 controls with angiographically normal coronary arteries were prospectively enrolled in the study. Genotypes were assessed using the polymerase chain reaction (PCR)-based restriction fragment length polymorphism (PCR-RFLP) technique.Results:Homozygote genotype for allele 2 of+3954 C>T 2/2 genotype was significantly more frequent in patients with CSFP than in the control group, whereas 1/2 genotype was more frequent in the control group (35.4% versus 14.5% for 2/2 genotype and 25% versus 35.5% for 1/2 genotype in CSFP and control groups, respectively, X2=6.6; p=0.04). The allelic frequency of allele 2 of this polymorphism was significantly higher in the CSFP group than in the control group (47.9% versus 28.6% in the control group, X2=5.6; p=0.02). However, there was no significant difference with regard to genotype or allelic frequencies of IL-1ra VNTR or IL-1β -511 SNP polymorphisms between patients with CSFP and controls.Conclusion:IL-1β+3954 SNP mutations are significantly more common in patients with CSFP. It may suggest that the tendency for inflammation may contribute to the presence of this phenomenon.

Interleukin-1 Gene Cluster Polymorphisms and Their Association with Coronary Artery Disease: Separate Evidences from the Largest Case-Control Study amongst North Indians and an Updated Meta-Analysis.

Several researchers have reported significant association of numerous single nucleotide polymorphisms (SNPs) residing in the interleukin-1 (IL-1) gene cluster with coronary artery disease (CAD). However, their association status amongst North Indian ancestry (NIA) have never been systematically assessed. Despite a published meta-analysis on this subject, their association status worldwide as well as amongst different major ancestral subgroups still remains unclear. We therefore decided to prospectively test the association of 11 IL-1 gene cluster SNPs with CAD, vide a case-control study amongst a cohort of NIA and attempted to validate our results with the help of an updated meta-analysis of all relevant published association studies. Included studies were segregated into ancestral subgroups and association statuses for each subgroup were determined. A total of 323 cases and 400 healthy, age and sex matched controls belonging to NIA were prospectively enrolled and subsequently genotyped for 11 selected IL-1 gene cluster SNPs. Although results for none of the evaluated IL-1 gene cluster SNPs reached the adjusted level of significance (p<0.0045), clear trends of association were seen for IL1B -511 C>T and IL1RN 86bp VNTR in several of the constructed genetic models (p range = 0.01–0.044 and 0.005–0.034 respectively). The presence of >1, ‘T’ (minor) allele of IL1B -511 C>T in a genotype seemed to provide protection against CAD (OR = 0.62, p = 0.044), while the presence of >1, ‘C’ (major) allele seemed to increase the risk of CAD (OR = 1.36, p = 0.041). The minor allele (allele 2) of IL1RN 86bp VNTR and its homozygous genotype (2/2 genotype) also seemed to carry an increased risk for CAD (OR = 1.62, p = 0.005 and OR = 2.25, p = 0.031 respectively). On the other hand, several haplotype combinations constructed out of IL1B and IL1RN gene variants clearly showed statistically significant associations with CAD (p<0.0045). Our meta-analysis was conducted for 8 previously assessed IL-1 SNPs. We included 53 different studies which involved a total sample of 26,210 (13,982 cases and 12,228 controls). Our pooled results concurred with the findings of our case-control study and was not able to deduce any statistically significant associations for any of the 8 studied SNPs (p>0.05). Subgroup analysis, however, yielded interesting results, where significant differences in association statuses were seen for IL1A +4845 G>T, IL1B -511 C>T, IL1RN 86bp VNTR and IL1RN +8006 T>C for select ancestral subgroups. The hints of associations deduced for subjects belonging to NIA in our case-control study for both IL1B -511 C>T and IL1RN 86bp VNTR were duly validated vide significant p values seen for NIA in all three genetic models (OR range = 0.62–0.76, p range = 0.01–0.04 and OR range = 1.51–2.25, p range = 0.004–0.04 respectively). On the other hand, Mixed Ancestry (MA) subgroup carrying IL1B -511 C>T, IL1RN 86bp VNTR or IL1RN +8006 T>C polymorphisms seemed to enjoy significant protection against CAD. A few other ancestral subgroups also demonstrated significant associations for a few of the studied SNPs vide one of the three genetic models. Clinical interpretation of derived results is however recommended.

Association of interleukin-1 gene cluster polymorphisms and haplotypes with multiple sclerosis in an Iranian population

Multiple sclerosis (MS) is a multi-factorial autoimmune disease of the central nervous system. The exact etiology of MS is still unknown. Due to the important roles that cytokines play as mediators in immune and inflammatory responses, we have evaluated the association of IL-1 gene cluster polymorphisms and haplotypes with MS susceptibility in 306 unrelated MS patients and 312 healthy matched controls. A significant association was found for the IL-1β +3953 T allele [OR=1.43, 95% CI (1.14–1.79), P value=0.002, Pc=0.01] and for IL-1β +3953 T/T genotype and MS risk [OR=1.92, 95% CI (1.25–2.96), P value=0.005, Pc=0.01]. Interestingly, the genotypes of the polymorphisms remained significant under recessive, co-recessive and dominant models. However, no significant differences were found between MS patients and controls in the genotype and allele frequencies of the IL-1β −511, −31 and IL-1Ra polymorphisms. Haplotype analysis for IL-1β −31 and IL-1β −511, with moderate linkage disequilibrium (LD), using the EM algorithm revealed a significant global association of haplotype differences between the two groups. Lower presence of two haplotypes (H3: C-T and H4: T-C) was observed in the MS patients than healthy controls. However, after applying Bonferroni's correction the differences were not significant. To our knowledge, this is the first study reporting the association of the IL-1β +3953 gene polymorphism and MS susceptibility.

Association analysis of the IL-1 gene cluster polymorphisms with aggressive and chronic periodontitis in the Algerian population

ObjectiveThere is strong evidence that genetic as well as environmental factors affect the development of periodontitis. Various studies suggest that genetic polymorphisms of the interleukin-1 (IL-1) genes are associated with an increased risk of developing the pathogenesis. The aim of the present study was to investigate the possible relationship between two polymorphisms of IL-1 gene cluster IL-1B (C+3954T) (rs1143634) and IL-1A (C−889T) (rs1800587) SNPs and the aggressive and chronic periodontitis risk in a case control study in Algerian population. Methods279 subjects were recruited and received a periodontal examination: 128 healthy controls and 151 cases. From cases, 91 patients were having a chronic disease whereas 60 subjects with aggressive form. All these subjects were genotyped for IL-1A (C−889T) and IL-1B (C+3954T) polymorphisms using TaqMan real time PCR technology. Frequencies of IL-1 alleles, genotypes and the haplotypes were also examined. ResultsSignificant differences were found in the carriage rate of both minor alleles of the IL-1A (C−889T) and IL-1B (C+3954T) polymorphisms of aggressive periodontitis cases compared with healthy controls (OR [95%CI]=1.61 [1.03–2.49], p=0.03), (OR [95%CI]=1.69 [1.09–2.63], p=0.01), respectively. The result did not reach significance with the chronic form. ConclusionThe studied polymorphisms of the IL-1 genes appear to be associated with susceptibility to aggressive periodontitis (AgP) in the Algerian population.

Interleukin-1 Gene Cluster Polymorphisms and its Haplotypes may Predict the Risk to Develop Cervical Cancer in Tunisia.

Our study aimed to evaluate the association between IL-1α (4845 G/T), IL-1β (-511C/T) and IL-1RN (VNTR) polymorphisms and risk of cervical cancer. This case-control study investigates three polymorphisms in 130 patients and 260 controls by PCR-restriction fragment length polymorphism (RFLP). The IL-1RN (VNTR) A1/A3 genotype appear as a cervical cancer risk factor (p = 0.048; OR = 2.92; 95 % CI = 1.00-8.74), moreover, the L/2* decreased the risk (p = 0.011; OR = 0.47; 95 % CI = 0.25-0.88) and may be a protective factor against this pathology. Stratified analysis according to the FIGO stage subgroup revealed that the IL-1β-511 T/T genotype and T allele may be a protective factors against cervical cancer development for patients with early stage (p = 0.030; OR = 0.46; 95 % CI = 0.22-0.96) (p = 0.020; OR = 0.68; 95 % CI = 0.48-0.97). However, for the patients with advanced FIGO stage, IL-1RN-VNTR L/2* genotype appear as a protective factor for this pathology (p = 0.023; OR = 0.29; 95 % CI = 0.08-0.99). The (G-T-L) haplotype showed a significant decreased frequency in cervical cancer patients as compared to controls (p = 0.032; OR = 0.53; 95 % CI = 0.29-0.95). In contrast, the (T-T-2*) combination appear a risk factor for the development of cervical cancer (p = 0.018; OR = 1.57; 95 % CI = 1.07-2.30). Our study suggested that IL1 cluster polymorphisms and haplotypes may be a genetic risk factor for cervical cancer.

Influence of Interleukin-1 Gene Cluster Polymorphisms on the Susceptibility and Outcomes of Acute Stroke in Egyptian Patients

Interleukin-1 (IL-1) has pleiotropic actions in the central nervous system. A growing corpus of evidence has indicated an important role of this cytokine in the development of brain damage following cerebral ischemia. The objective of this study is to investigate the influence of IL-1 cluster gene polymorphisms on the susceptibility of acute stroke and its outcomes in Egyptian patient. 320 patients with new or recurrent stroke [176 with atherothrombotic cerebral infarction, 79 with intracerebral hemorrhage (ICH), and 65 with subarachnoid hemorrhage (SAH)] and 320 controls were included in the study. IL-1b -511, IL-1a -889, and IL-1RN VNTR polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism. Serum level of IL-1 was measured by enzyme linked immunosorbent assay. All patients were followed for neurological and functional impairments 7 days, 1, 3 and 6 months after the onset of the stroke. We found that IL-1b -511 gene polymorphisms were significantly increased in patients with atherothrombotic, intracerebral, and SAH. Subjects with IL-1a -889 CT and TT genotypes were significantly more likely to have atherothrombotic infarction. Both IL-1b -511, IL-1a -889 genes polymorphisms were significantly more likely to have severe neurological and functional impairment, while IL-1RN 2/2 genotype was significantly decreased in atherothrombotic infarction and ICH groups and showed less severe neurological and functional impairments 7 days, 1, 3, and 6 months after the onset of the stroke compared with carriers of the IL1RN 1/1 and 1/2 genotypes. We concluded that IL-1 cluster gene polymorphisms were associated with risk of acute stroke. IL-1b, IL-1a gene polymorphisms were associated with more severe functional and neurological impairments, while IL-1RN VNTR polymorphisms were associated with good outcomes.

Interleukin-6, interleukin-1 gene cluster and interleukin-1 receptor polymorphisms in Iranian patients with juvenile systemic lupus erythematosus.

Juvenile systemic lupus erythematosus (JSLE) is a polygenic, autoimmune disorder of unknown origin. As proinflammatory cytokines, including interleukin-6 (IL-6) and the interleukin-1 (IL-1) family, seem to contribute to the pathogenesis of JSLE, this investigation was performed to assess the associations of particular single nucleotide polymorphisms (SNPs) of IL-6 and IL-1 genes in a case-control study. Fifty nine JSLE cases were recruited for this study as the patient group, and were compared against 140 healthy, unrelated, control subjects. Using the polymerase chain reaction with the sequence-specific primer method, genotyping was carried out for the IL-6 gene at positions -174 and nt565, as well as the IL-1α gene at position -889, the IL-1β gene at positions -511 and +3962, the interleukin-1 receptor (IL-1R) gene at position Pst-I 1970, and the interleukin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100. RESULTS of the analyzed data revealed a remarkable, positive association for the promoter sequence of the IL-1β gene at position -511 for T/T in the patient group compared with healthy controls (P value, 0.03). Furthermore, a significant negative association was found between the T/C genotype at the same position on the IL-1β gene in juvenile SLE (P value, 0.03). cytokine gene polymorphisms might play a role in the pathophysiology of JSLE. Particular IL-1 gene variants could affect individual susceptibility to JSLE.

Interleukin-1 gene cluster and IL-1 receptor polymorphisms in Iranian patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology with a complex pathogenesis involving multiple genetic and environmental contributions. Single-nucleotide polymorphisms (SNPs) in cytokine genes are associated with higher or lower cytokine activity, which can alter the susceptibility to certain diseases or their clinical outcomes. We investigated SNPs of the IL-1 family in Iranian SLE patients and normal individuals. We obtained blood samples from 207 SLE patients and 213 healthy controls. Cytokine genotyping was performed by polymerase chain reaction with sequence-specific primers. The following SNPs were assessed: IL-1A rs1800587, IL-1B rs16944 and rs1143634, IL-1R1 rs2234650 and IL-1RN rs315952. The frequency of the IL-1RN rs315952 CT genotype was significantly lower among patients with SLE compared with healthy controls (OR = 0.63, 95 % CI = 0.42-0.95; P < 0.05 relative to reference genotype and OR = 0.62, CI = 0.42-0.93; P < 0.05 relative to homozygous genotypes). For all other studied alleles and genotypes, there were no significant differences concerning genotype frequencies between patients and controls. A significant increase in IL-1RN rs315952 T allele frequency was noted in patients with a hematologic manifestation (OR = 1.75; 95 % CI = 1.07-2.84; P = 0.033). Polymorphism in IL-1RN rs315952 was significantly associated with SLE in Iranian patients, rs315952CT genotype being a protective factor. We found that IL-1RN rs315952 T allele frequency was significantly higher in patients with hematologic manifestations. Variation at this locus may affect IL-1 receptor antagonist activity, supporting the hypothesis that altered or imbalanced IL1 production may affect the risk of developing SLE.

The Interleukin-1 Gene Cluster Polymorphisms Are Associated with Takayasu's Arteritis in Mexican Patients

Takayasu's arteritis (TA) is a chronic inflammatory arteritis of unknown etiology involving mainly the aorta and its major branches. The interleukin (IL) 1β and IL-1 receptor antagonist have been playing an important role as regulators of inflammation. We investigated whether the polymorphisms at the IL-1B and IL-1RN gene cluster were associated with the genetic susceptibility to develop TA. We analyzed the IL-1B, IL-1F10.3, and IL-1RN polymorphisms in a sample of 58 TA patients, and 248 clinically healthy unrelated Mexican individuals by 5' exonuclease TaqMan polymerase chain reaction. Polymorphic haplotypes were constructed after linkage disequilibrium analysis. We found increased frequencies of different polymorphisms (C allele and TC genotype of IL-1F10.3; TT genotype of IL-1RN.4; C allele and TC genotype of IL-1RN6.1; G allele of IL-1RN6.2 and haplotypes "1T" and "1C" of IL-RN VNTR and IL-1RN6.1) in the group of TA when compared to healthy controls. On the other hand, decreased frequency of IL-1-511 TC genotype was found in the TA group compared to controls. IL-1B and IL-1RN gene polymorphisms could be involved in the risk of developing TA in the Mexican population. These associations were independent of the affected vessels.

Lack of Association of Interleukin-1 Gene Cluster Polymorphisms with Angiographically Documented Coronary Artery Disease: Demonstration of Association with Hypertension in the Polish Population

Inflammation plays a key role in the development of atherosclerosis. We investigated associations between the interleukin-1β gene (IL1B) and IL-1 receptor antagonist (IL1RN ) polymorphisms and their haplotypes, with coronary artery disease (CAD), severity of CAD (single vessel, SVD vs. multivessel disease, MVD) and hypertension. Three hundred eighteen individuals were submitted to coronary angiography. Of these, 201 patients with ≥50% occlusion in at least one major coronary artery comprised the CAD group; the control group (non-CAD) consisted of the remaining 117 subjects. The genotypes of IL1B C(-31)T and IL1RN VNTR were determined by polymerase chain reaction (PCR). Allele (-31)C of the IL1B gene was significantly associated with hypertension (p= 0.046). There was no association of hypertension with IL1RN genotype. The association between the number of IL1B C alleles and prevalence of hypertension was similar in univariate (OR 1.383; 95% CI 1.002-1.909; p= 0.048) and multivariate (OR 1.429; 95% CI 1.021-1.999; p= 0.036) analysis. We did not observe a significant association between CAD and genotypes or alleles of IL1B C(-31)T/IL1RN VNTR or their haplotypes. No associations were found between IL1B C(-31)T or IL1RN VNTR genotypes, alleles or haplotypes and the severity of CAD when subgroups with SVD and MVD were compared. No association was found between polymorphisms of IL1B C(-31)T/IL1RN VNTR or their haplotypes and CAD. However, the data suggest that allele (-31)C of IL1B may be a risk factor for hypertension in the Polish population with CAD in the western Pomeranian region of Poland.

Single nucleotide polymorphisms in interleukin-1gene cluster and subgingival colonization with Aggregatibacter actinomycetemcomitans in patients with aggressive periodontitis

Periodontitis is initiated by the subgingival occurrence of periodontopathogens. It is triggered by a specific host-dependent immune response that is influenced by genetic predisposition. Polymorphisms in the interleukin-1 (IL-1) gene cluster have been suggested to influence the pathogenesis of periodontitis. A total of 159 periodontitis patients (chronic disease: n = 73, aggressive disease: n = 86) and 89 periodontitis-free controls were included in the study. Polymorphisms IL-1α (rs1800587), IL-1β (rs16944, rs1143634), IL-1 receptor (rs2234650), and IL-1 receptor antagonist (rs315952) were determined by polymerase chain reaction with sequence-specific primers (PCR-SSP). Subgingival bacterial colonization was assessed using a polymerase chain reaction/DNA probe test (micro-Ident). Haplotype block structure was determined using Haploview 4.2. Statistical analyses were performed applying SPSS 17.0 considering dominant, recessive, and codominant genetic models. In this case-control study, no association between genomic variants of the IL-1 gene cluster and the incidence of severe periodontitis could be shown. Carriers of the rare genotypes of rs1800587 ( p corr = 0.009), rs1143634 ( p corr = 0.009) and composite genotype (rs1800587+rs1143634) ( p corr = 0.031) had a twofold higher risk for subgingival occurrence of Aggregatibacter actinomycetemcomitans. In forward stepwise binary logistic regression analyses considering age, gender, smoking, and approximal plaque index as potential confounders these significant associations were demonstrated. Despite the genetic background of IL-1 gene cluster could be shown to be associated with subgingival colonization of A actinomycetemcomitans, there is no evidence that it is an independent risk indicator for periodontitis.

Investigation of the interleukin-1 gene cluster polymorphisms in Jordanian patients with chronic and aggressive periodontitis

Objective Interleukin-1 (IL-1) is a proinflammatory cytokine that is highly elevated in response to bacterial biofilms and is a potential risk factor for periodontal diseases. IL-1 gene polymorphisms have been associated with the IL-1 level. The aim of this study was to investigate if IL-1 gene cluster polymorphisms are associated with chronic (CP) and aggressive (AgP) periodontitis in a Jordanian population. Methods A total of 100 CP, 80 AgP patients and 80 controls were genotyped using PCR for IL-1RN-86-bp VNTR and PCR-RFLP for IL-1A-889, IL-1B-511, -35, +3953, and IL-1RN +8006, +9589, +11100 SNPs. The distribution of alleles and genotypes between groups was compared using χ 2 analysis. Estimation of haplotype frequencies was carried out using the EH programme. Results The IL-1RN8006 SNP and the IL-1RN-VNTR were associated with CP but not with AgP. The C allele and TC genotype of IL-1RN8006 were increased in CP ( P corr = 0.002, 0.00026 respectively). The A1 allele and A1/A1 genotype of the IL1-RN-VNTR were significantly increased in CP ( P corr = 0.0007, <0.0001 respectively). The CA1 haplotype formed by both markers was present in 29 CP patients but not in any of the controls ( P < 0.0001). No significant differences were found in the distribution of allele and genotype frequencies of the other markers between CP and AgP cases and controls. Conclusions IL-1RN 8006 and IL-1RN VNTR were associated with CP but not AgP in a Jordanian population, whilst other investigated markers in IL-1A, IL-1B and IL-1RN were not associated with either CP or AgP.

Lack of Association between Interleukin-1 Gene Cluster Polymorphisms and Glaucoma in Chinese Subjects

A recent study identified single nucleotide polymorphisms (SNPs) within the IL-1 gene cluster at chromosomal locus 2q13 that were associated with reduced risk for primary open-angle glaucoma (POAG) in whites. The purpose of this study was to investigate the association between IL-1 SNPs and glaucoma in Chinese patients with either POAG or primary-angle closure glaucoma (PACG). Patients with POAG with a mean IOP without treatment that was consistently <21 mm Hg on diurnal testing were classified as having normal-tension glaucoma (NTG) and those with higher IOP were classified as having high-tension glaucoma (HTG). Subjects with PACG had at least 180 degrees of angle closure on gonioscopy. Genotypes were determined by polymerase chain reaction and restriction digest enzymes at the following loci: IL1A (-889C/T), IL1B (+3953C/T), and IL1B (-511C/T). The association of individual SNPs with glaucoma was evaluated by using chi(2) testing. Haplotype analysis was performed with the PHASE program, with haplotype frequency estimated for combined cases and controls, assuming Hardy-Weinberg equilibrium (HWE) of haplotypes. Of the Chinese subjects studies, 194 had POAG (94 NTG and 100 HTG), 125 had PACG, and 79 were normal control subjects. There was no significant difference in IL-1 SNP or allele frequencies for in subjects with POAG or PACG compared with control subjects, or between NTG and HTG. None of the common haplotypes showed any significant difference between the HTG, NTG, PACG, and normal control subjects. This study did not find an association between IL-1 gene cluster polymorphisms and glaucoma in this sample of Chinese subjects.

Speed of tooth movement is related to stress and IL-1 gene polymorphisms

The variables affecting speed of tooth movement are unquantified. In particular, the effects of stress and human biological variations are unknown. Therefore, our objectives in this study were to determine relationships between (1) stress and velocity of tooth translation (v(t)), and (2) interleukin-1 (IL-1) gene cluster polymorphisms, IL-1beta and IL-1 receptor antagonist (IL-1RA) in gingival crevicular fluid (GCF), and v(t). Ten subjects had their maxillary first premolars extracted and cheek wipe samples genotyped. In each subject, a maxillary canine received 26 kPa and the other received 13 or 52 kPa of stress. GCF samples and tooth movements were measured at 9 or 10 visits over 84 days. Mean v(t) for canines retracted by 13, 26, and 52 kPa were 0.054, 0.072, and 0.064 mm per day, respectively. Faster v(t) was shown from 26 kPa than 13 kPa (P = .015) and 52 kPa (P = .030), with higher IL-1beta/IL-1RA in GCF at experimental relative to control sites, and in subjects with homozygosity for allele 1 (A1,A1) compared with at least 1 copy of A2 (A2+) at IL-1RN(VNTR(86 bp)) (P = .032), and with A2+ compared with A1,A1 at IL-1B(+3954) (P = .051). Stress, IL-1beta/IL-1RA in GCF, and IL-1 gene cluster polymorphisms are related to v(t).

Association of interleukin-1 gene cluster polymorphisms with ischemic stroke in a Chinese population

Chronic inflammatory process plays an important role in atherothrombosis. Interleukin-1 (IL-1) is one of the key modulators of the inflammatory response and its activity is critically regulated by its receptor antagonist (IL-1Ra). A variable number tandem repeat polymorphism in intron 2 of IL-1Ra gene and a C to T single base polymorphism in the promoter of IL-1beta gene (C(-511)-->T) have been reported to affect the levels of IL-1 as well as its antagonist, IL-1Ra. It is also reported in several studies that these polymorphisms are associated with the susceptibility to cardio-cerebral vascular disease. However, data are limited in China. In this article, we studied the relationships between these polymorphisms and the risk of ischemic stroke in China. One hundred and twelve patients committed ischemic stroke were compared with 95 demographically matched healthy volunteers. The frequencies of the IL-1Ra 1/1 genotype and IL-1Ra allele 1 (Ra*1 allele) in stroke patients were significantly higher than those in healthy volunteers [93.7% vs. 82.1%, P =0.014; 0.964 vs. 0.905, P =0.007]. No significant differences were found in the IL-1beta -511 genotype and the allele distribution between the two groups. Our results implicated that IL-1 gene polymorphism might be associated with the susceptibility to ischemic stroke.

IL1RN Polymorphism and cagA-Positive Helicobacter pylori Strains Increase the Risk of Duodenal Ulcer in Children

Duodenal ulcers in children are associated with Helicobacter pylori gastric infection with cagA-positive strains, but factors linked to the host are poorly known. The authors evaluated the role of proinflammatory interleukin-1 gene cluster polymorphisms in the pathogenesis of duodenal ulcer. They studied prospectively 437 children 1 to years old, 209 of whom were H. pylori positive and 228 of whom were H. pylori negative. IL1B-511-C/T, -31T/C, and IL1RN Variable number of tandem repeats were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism, PCR with confronting two-pair primers, and PCR, respectively. cagA status was evaluated by PCR. The role of the proinflammatory cytokine genotypes in the genesis of duodenal ulcer was evaluated before and after stratification of H. pylori status on logistic regression models. In the group of children without duodenal ulcer, no association was observed between H. pylori status and proinflammatory polymorphisms. Furthermore, no association between IL1 cluster genotypes and cagA status was seen in the H. pylori-positive children. However, increasing age, male sex, and IL1RN*2 were independently associated with duodenal ulcer. After stratification, in the H. pylori-positive children, increasing age, male sex, the presence of ILRN*2 allele, and cagA-positive status were independently associated with duodenal ulcer. The risk for the development of duodenal ulcer increased when a combined association of the presence of IL1RN*2 allele and infection by a cagA-positive H. pylori strain was the variable. This study provides evidence supporting independent roles of IL1RN*2 allele and cagA-positive status in the genesis of duodenal ulcer in children.

Interleukin-1 Gene Cluster Polymorphisms Are Associated with Nutritional Status and Inflammation in Patients with End-Stage Renal Disease

Background: Wasting and inflammation are two common risk factors for death in patients with end-stage renal disease (ESRD). Interleukin-1β (IL-1β) and its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of wasting and inflammation. Methods: To investigate effects of the IL-1 gene cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients (52 ± 12 years, 62% males) close to the start of renal replacement therapy. 205 healthy volunteers served as controls. We analyzed the IL-1B –511C/T, –31C/T, and +3954C/T polymorphisms as well as a variable number of a tandem repeat (VNTR) in IL-1RN. Nutritional parameters included serum albumin level, subjective global nutritional assessment (SGA), and body composition evaluated by dual-energy X-ray absorptiometry (DXA). We used serum high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation. Results: Wasting (SGA >1) was present in 31%, whereas inflammation (CRP ≧10 mg/l) was present in 36% of the patients. The male carriers of the –511T/T and –31C/C genotypes had a lower prevalence of wasting (p < 0.05), higher body mass index (BMI) (p < 0.05), and higher lean body mass (LBM) (p < 0.01). In a stepwise multiple regression model, age (p < 0.05), BMI (p < 0.01) and the IL-1B –511 genotype (p < 0.01) were independently associated with LBM. The carriers of the +3954T allele had a lower prevalence of inflammation (p < 0.05) and lower serum hsCRP (p < 0.05). The VNTR in IL-1RN was not associated with any markers. Conclusion: The investigated IL-1 gene cluster polymorphisms were associated with nutritional status and inflammation in ESRD patients, but marked differences were found between the genders. These polymorphisms could have prognostic utility for predicting wasting and inflammation in ESRD patients.

Interleukin-1 gene cluster polymorphisms predict risk of ESRD

Patients with chronic kidney disease manifest an inflammatory state relative to healthy individuals. Inflammation is regulated in part by genes of the interleukin-1 (IL-1) gene cluster. We hypothesized that polymorphisms in this gene cluster may be associated with risk of end-stage renal disease (ESRD). Polymorphisms in the IL-1 gene cluster were examined in a cohort of 239 racially diverse hemodialysis (HD) patients and 252 controls. These individuals were genotyped for 3 single nucleotide polymorphisms (SNPs) in the IL-1alpha and beta genes, and a variable-number-of-tandem-repeats polymorphism in the IL-1 receptor antagonist gene (IL-1RN). Polymorphisms were analyzed by logistic regression for their independent associations with ESRD, and the effect of allele dose of IL-1RN on risk for ESRD was examined. The interaction between race and genotype was also investigated. A logistic regression model demonstrated that homozygosity for allele 2 of the IL-1RN variable-number-of-tandem-repeats (VNTR) polymorphism was associated with ESRD independent of race (P < 0.0005). The IL-1alpha-889 promoter SNP was associated with ESRD independent of race and of the IL-1RN polymorphism (P= 0.04). The IL-1beta-511 promoter SNP is associated with ESRD, but this is accounted for by race (P= 0.04). Two polymorphisms within the IL-1 gene cluster are associated with ESRD independent of race. This finding is one of the strongest associations between genotype and ESRD reported, and suggests that polymorphisms in the IL-1 gene cluster affect the risk of development of ESRD.

W13-P-011 Interleukin-1 gene cluster and interleukin-6 gene polymorphisms and increase in C-reactive protein levels in patients with acute coronary syndrome

The 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.A 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 24 h 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.PLBW 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).Our 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.

Association Analysis of Interleukin-1 Gene Cluster Polymorphisms with Ischemic Stroke in a Chinese Population.

Chronic inflammatory process acted an important role in atherothrombosis. Interleukin-1 (IL-1) is one of the key modulators of the inflammatory response, and its activity is critically regulated by its receptor antagonist (IL-1ra). Recently, several interleukin-1 cluster gene polymorphisms may associated with acute coronary syndrome have been reported, although with contrasting results. The associations of a variable number tandem repeat (86bp) polymorphism in intron 2 of IL-1ra and of the -511C/T polymorphism of IL-1β with the risk of the ischemic stroke were studied. 112 ischemic stroke patients of Chinese ancestry studied within ten days after presentation were compared with 95 ethnically matched healthy volunteers. 56 among these 112 stroke patients were followed for six months to have prognosis evaluated through measuring Modified Rankin Scale (RS) and Barthel Index (BI). 60 stroke patients had measured the plasma IL-1ra and C-reative protein (CRP) values. The frequency of the IL-1RN 1/1 genotype in the 112 stroke patients was significantly higher than those in healthy volunteers (93.7% vs 82.1%, p<0.05). The frequency of the IL-1RN allele 1 in the 112 stroke patients was significantly higher than those in healthy volunteers (96.4% vs 90.5%, p<0.01, OR=3.23, 95% CI 1.32–7.91). No significant association was seen for the IL-1β-511 C/T polymorphism. In the six months followed group, IL-1RN1/2 genotype carriers had higher BI scores compared with IL-1RN1/1 genotype carriers (98.00 vs 84.80, p<0.01), and patients with lower plasma IL-1ra value (below the median value 186.55pg/ml) had higher BI scores (95.00 vs 77.19, p<0.05), but no significant influence of CRP values and IL-1ra on prognosis or showed no significantly association on plasma IL-1ra and CRP values with IL-1β-511 C/T or IL-1RN genotpye studied in stroke patients. Our results implicate the IL-1ra gene in the susceptibility to ischemic stroke, which may be a useful clue for pharmacological intervention in IL-1 production.