白细胞介素-1基因多态性与高血压易感性的研究

目的　观察白细胞介素 - 1(interleukin- 1,IL- 1)基因多态性在中国汉族人群中的分布及其与原发性高血压 (essential hypertension,EH)的关系 ,初步分析其基因型与 EH易感性的相关性。方法　应用聚合酶链反应和限制性片段长度多态性的方法 ,检测湖北省汉族 15 2例 EH患者和 16 8名正常对照者的IL- 1基因多态性 ,包括 IL- 1α(- 889C/ T)位点、IL- 1β(- 5 11C/ T)位点、IL- 1β( 395 3C/ T)位点、IL- 1Ra( 80 0 6 T/ C)位点多态性以及 IL- 1Ra第 2内含子可变数串联重复序列多态性。结果　IL- 1α(- 889C/ T)位点、IL- 1β( 395 3C/ T)位点、IL- 1Ra( 80 0 6 T/ C)位点多态性和 IL- 1Ra可变重复序列多态性在 EH组和正常人群中的分布差异无显著性 (P>0 .0 5 ) ,而 IL- 1β(- 5 11C/ T)位点多态性在两组人群中的分布差异存在显著性 (P<0 .0 5 ) ,携带 CT基因型罹患 EH的危险性可增加 2 .5 4倍。结论　 IL- 1β基因启动子区 - 5 11位点 C/ T多态性可能与 EH易感性存在相关关系。     

Polymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson's disease

Several lines of evidence indicate that immune mechanisms are involved in the pathogenesis of neurodegenerative disorders. Activated immunocompetent cells and inflammatory cytokines are present in affected brain regions in patients with Alzheimer's (AD) and Parkinson's disease (PD). For AD biochemical and pathological data are supported by genetic studies identifying risk alleles for polymorphisms in regulatory regions of the interleukin-1 alpha (IL-1 alpha-889) and interleukin-1 beta (IL-1 beta-511) gene, respectively. The partially overlapping pathology and inflammatory reaction pattern between AD and PD led us to investigate these polymorphisms in a large sample of 295 German PD patients and 270 healthy controls. We found T in position -511 in the IL-1 beta gene more frequent in patients compared to controls (chi(2)=4.44, P=0.034). For the IL-1 alpha-889 polymorphism no significant difference between patients and controls was observed.     

IL1 Gene Cluster Polymorphisms and Its Haplotypes may Predict the Risk to Develop Invasive Pulmonary Aspergillosis and Modulate C-reactive Protein Level

OBJECTIVE: The aim of this study was to determine whether interleukin-1 alpha (IL1alpha), interleukin-1 beta (IL1beta), and IL1 receptor antagonist (IL1Ra) polymorphisms are implicated in invasive pulmonary aspergillosis (IPA) pathogenesis. MATERIALS AND METHODS: Subjects comprised 110 hematological patients and 148 healthy controls. Genotypic and allelic frequencies were similar between hematological patients and controls. IPA was diagnosed in 59 of the 110 patients according to consensus criteria published by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/IFICG). RESULTS AND DISCUSSIONS: Individual locus analysis showed that IL1alpha and IL1Ra polymorphisms were not associated with the presence of IPA (p = 0.560 and p = 0.680, respectively). However, a trend towards a higher presence of IL1beta( - ) (511TT) genotype (or IL1beta(-511T) allele) in the IPA group than in the non-IPA patient group (p = 0.092 and p = 0.095, respectively) was found. Haplotype analysis revealed that VNTR2/-889C/-511T haplotype was strongly associated with susceptibility to develop IPA infection (p = 0.020). Haplotype analysis also showed an association between VNTR2/-889C/-511C haplotype and resistance to IPA infection (p = 0.028). Furthermore, patients with IL1Ra VNTR2/2 and IL1beta(-511)T/T genotypes had a higher positive serum galactomannan percentage versus patients with other genotypes. Finally, C-reactive protein (CRP) production was significantly associated with IL1 gene cluster polymorphisms, although CRP values were similar between IPA and non-IPA groups. CONCLUSION: These findings indicate a critical role of IL1 gene cluster polymorphisms in the susceptibility to IPA infection and CRP production.     

Environmental factors and not genotype influence the plasma level of interleukin-1 receptor antagonist in normal individuals

Cytokine production may be regulated by both genotypic (single nucleotide or tandem repeat polymorphisms) and non-genotypic factors relating to the environment and inherent biology (i.e. gender). Interleukin (IL)-1 is one of the body's most highly proinflammatory cytokines and is implicated in the pathophysiology of numerous diseases, but also in the maintenance of homeostasis in a number of tissues. The cytokine IL-1 receptor antagonist (IL-1Ra) is the competitive inhibitor of the IL-1 agonists IL-1alpha and IL-1beta. In vivo IL-1Ra was measured in a cohort of 200 + blood donors and the effect of the IL-1 gene polymorphisms, environmental and biological factors assessed. In this study, we observed that possession of particular alleles of 5 IL-1 gene polymorphisms (IL1A-889, IL1Alpha VNTR, IL1B -511, IL1B +3953 and the IL1RN VNTR) did not correlate with higher plasma IL-1Ra levels. Environmental factors such as smoking and non-steroidal anti-inflammatory drug ingestion were associated with higher in vivo IL-1Ra levels (P = 0.015 and 0.022, respectively), but biological factors such as gender, age and menstruation status did not have any impact upon in vivo IL-1Ra levels. Genotypic associations of IL-1 gene family polymorphisms with disease features may reflect characteristics of stressed rather than normal control circuits for cytokine production.     

Genetic analysis of interleukin-1 receptor antagonist and interleukin-1β single-nucleotide polymorphisms C−511T and C+3953T in alopecia areata: susceptibility and severity association

The present study was aimed to explore the effect of two selected polymorphisms from interleukin-1β (IL-1β) gene [SNPs ?511 and +3953] and a variable number of tandem repeat (VNTR) from interleukin-1 receptor antagonist (IL-1RN) on the susceptibility and severity of alopecia areata (AA) in Kuwaiti subjects. IL-1β SNPs C?511T, C+3953T, and IL-1RN VNTR were screened in 96 alopecia patients classified clinically, according to the disease severity as patchy (P), semiuniversalis (SU), and universalis (U), and in 100 ethnically matched healthy controls. Polymerase chain reaction followed by restriction fragment length polymorphism and direct DNA sequencing were employed for genotyping. Comparing the stratified AA cases based on severity, IL-β SNP C?511T showed a significant association (genotype and allelotype levels p = 0.03 and p = 0.028, respectively). Genotype CC was 50 % more frequent in U cases than in P or SU. When P and SU were grouped and tested against U, a significant difference was observed (genotype and allelotype levels p = 0.006 and p = 0.008, respectively). Compared to genotype CT, carriers of IL-1β ?511 CC genotype showed an increased risk to develop severe AA (p = 0.004, OR = 4.14, 95 % CI = 1.61–10.69). Four alleles and genotypes (1/1, 1/3, 1/4, and 2/2) of IL-1RN VNTR were detected in AA patients while only two (1/1 and 1/3) in controls. IL-1RN VNTR showed genotype and allelotype association with AA (p = 0.05 and p = 0.025, respectively). Our results showed that IL-1β and IL-1RN VNTR are significantly associated with the susceptibility to alopecia areata. Allele C of the IL-β C?511T SNP is linked to the severe form of AA.     

Single nucleotide polymorphisms in intron 2 of the human interleukin-1 receptor antagonist (IL-1Ra) gene: further definition of the IL-1 beta and IL-1Ra polymorphisms in North American Caucasians and Taiwanese Chinese

Previous studies have suggested that a variable number tandem repeat (VNTR) polymorphism in the second intron of the interleukin-1 receptor antagonist (IL-1Ra) gene and the single nucleotide polymorphisms at positions -511 and +3954 of the IL-1beta gene might be associated with increased risks of chronic inflammatory diseases, autoimmune diseases and gastric cancer. In the present study, IL-1beta and IL-1Ra genotypes were analyzed among Asians in Taiwan and Caucasians in North America. We identified a novel polymorphism with 3 nucleotide substitutions in the IL-1Ra VNTR 2-repeat allele. One of the substitutions corresponds with the fourth 3' end nucleotide of the reverse primer that is often used for analysis of the IL-1Ra-associated VNTR locus. Mismatching between this primer and the 2-repeat allele can cause misleading amplification results when stringent conditions are used for annealing. The estimated haplotype frequencies of the variant IL-1 genes were significantly different between Taiwanese and Caucasians. The frequency of the pro-inflammatory IL-1Ra 2-repeat allele was significantly lower in Taiwanese than in Caucasians. In contrast, the frequencies of the pro-inflammatory IL-1beta -511T allele and +3954C allele were significantly higher among Taiwanese compared with Caucasians.     

Association between the interleukin-1alpha gene and Alzheimer's disease: a meta-analysis

Inflammatory processes are involved in the pathogenesis of Alzheimer's disease (AD). Several studies have addressed the effects of interleukin-1 (IL-1) genes polymorphisms on the risk of developing AD. The results are not in full agreement on whether these polymorphisms are associated with the disease. To clarify this issue, we performed a meta-analysis of all the association studies between IL-1 genes and AD. Due to the relatively small number of published articles, the meta-analysis was restricted to the association of the IL-1alpha -889 C/T gene polymorphism and AD. Under a random effects model, the risk for the disease was significantly higher in subjects with the T/T genotype in comparison with both C/T (OR: 1.51; 95% C.I.: 1.15-1.99) and C/C (OR: 1.49; 95% C.I.: 1.09-2.03) subjects. There was modest heterogeneity for these effect estimates. Analysis of subgroups showed a significant association in patients with early-onset AD but not in late-onset AD. Our data support a significant but modest association between the T/T genotype of the IL-1alpha gene and AD.     

Lack of association between human longevity and polymorphisms of IL-1 cluster, IL-6, IL-10 and TNF-alpha genes in Finnish nonagenarians.

There has been increasing interest in research on genetic basis of longevity. Aging is accompanied by immune deterioration and dysregulation of cytokines. Increased IL-6 concentration in vivo and enhanced IL-6, IL-1beta, and TNF-alpha production in vitro have been reported in healthy elderly people. Cytokine gene polymorphisms have been demonstrated to be associated with cytokine production both in vivo and in vitro, and with some diseases. Thus, gene polymorphisms of cytokine may play a role in longevity by modulating an individual's responses to life-threatening disorders. Cytokine gene polymorphisms at IL1A-889, IL1B+3953, IL1B-511, IL1RN VNTR, IL6-174, IL10-1082, and TNFA-308 were genotyped in 250 Finnish nonagenarians (52 men and 198 women) and in 400 healthy blood donors (18-60 years) as controls. No statistically significant differences were found in the genotype distributions, allelic frequencies and A2+ carrier status of IL-1alpha, IL-1beta, IL-1RA, IL-6, IL-10, and TNF-alpha genes between nonagenarians and younger controls within Finnish population, nor between male and female nonagenarians. No differences emerged between nonagenarians and younger controls by comparing different IL-1 gene cluster haplotypes. Thus, there is no evidence of an association of IL-1 complex, IL-6, IL-10, and TNF-alpha gene polymorphisms with longevity, alone or in combination.     

Association of an interleukin-1beta gene polymorphism at position -511 with Alzheimer's disease

Inflammation is thought to promote neuronal cell death in Alzheimer's disease (AD). The proinflammatory interleukin-1 is a main component in inflammatory pathways and is overexpressed in the brain of AD patients. Investigation of different polymorphisms in the interleukin-1 genes (IL-1alpha -889, IL-1beta -511, IL-1beta +3953) revealed associations between specific alleles and AD in that they increased the risk or modified the age at onset of AD. However, there are controversial findings from other studies which revealed no significant associations between these polymorphisms and AD; thus further evaluation of the association of IL-1 gene polymorphisms with AD and their role in pathogenesis is needed. In this study we examined the distribution of the IL-1beta -511 alleles in AD patients and a control sample of healthy individuals. An additional control population of non-demented depressive inpatients was recruited to exclude a confounding bias. The cerebrospinal fluid (CSF) levels of Abeta42 in AD patients were investigated to assess the influence of IL-1beta -511 genotypes. We found no significant association of the IL-1beta -511 polymorphism with AD, suggesting that the IL-1beta -511 polymorphism is no risk factor for AD. However, we found the Abeta42 CSF levels to be lower in carriers of the IL-1beta CC-genotype compared to carriers of the T-allele. Even though IL-1beta -511 polymorphism did not influence the risk of AD it might have a pathophysiological influence on the disease process.     

Étude des polymorphismes des gènes de l’interleukine-1 et de l’antagoniste du récepteur de l’interleukine-1 chez des patients atteints de polyarthrite rhumatoïde

Objectives

One of the most important pro-inflammatory cytokines in the pathophysiology of rheumatoid arthritis (RA) is interleukin 1 (IL-1). The purpose of this study is to evaluate the association between IL-1B (-511), IL-1 (+3953), IL-1 RN variable number of tandem repeat (VNTR) polymorphisms and the occurrence in Algerian patients with rheumatoid arthritis. We also analyze their correlations with clinical and biological phenotypes.

Patients and methods

One hundred and forty-seven patients with RA (119 women, 28 men) and 127 controls (70 women, 57 men) were included in the study. The analysis of two polymorphisms of IL-1B-511 and IL-1B+3953 was done by PCR-RFLP. Analysis of IL1-RN VNTR polymorphism was performed by PCR.

Results

No significant difference in genotype, allelic and haplotype distribution at the three polymorphisms was observed between RA patients and controls. However, the genotype (T/T) polymorphism of IL-1B-511 is more frequent in the group of patients with positive ACPA compared with negative ACPA group (Pc = 0.01, OR = 4.65). Moreover, we noted that the haplotype (IL-1RN* 1/IL-1B-511T/IL-1B+3953C) was more frequent (Pc = 0.03, OR = 2.05) in the positive ACPA group.

Conclusion

The association between the allele 1 of IL-1 RN VNTR, T allele of IL1B-511 and C allele of IL1-B +3953 polymorphisms seems to predispose to the synthesis of ACPA and therefore to the occurrence of ACPA positive RA. Further studies with a larger number of patients are needed to define the real role of IL-1 in the susceptibility to or severity of RA.     

Association of interleukin-1 gene polymorphisms with dementia in a community-based sample: the Honolulu-Asia Aging Study

The interleukin-1 (IL-1) pro-inflammatory cytokine family participates in inflammatory processes and vessel damage involved in neurodegeneration. Recent studies suggest that Alzheimer's disease (AD) and vascular dementia (VaD) may share genetic risk factors. In this study, the frequency of polymorphisms in the genes coding for interleukin (IL)-1alpha, IL-1beta and the IL-1 receptor antagonist (RN) and their genotype associations with late-onset AD and VaD were determined in a Japanese-American cohort of men (n=931) participating in the Honolulu-Asia Aging Study (HAAS). A significant association was found between the IL-1beta (-511) and IL-1RN (+2018) polymorphisms and AD, suggesting that these variants confer an increased risk. Possessing the IL-1beta (-511) T/T genotype was also associated with VaD. There was no difference in the IL-1beta (+3953) frequency among the groups. Our results support the hypothesis that certain genetic variations contained within the IL-1 gene family contribute to the pathogenesis of dementia.     

IL-1 gene polymorphisms and genetic susceptibility of gallbladder cancer in a north Indian population

Long-standing gallstones are generally present in 65-80% patients of gallbladder cancer (GBC). It has also been suggested that inflammation caused by gallstones may be involved in the development of GBC. Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1 beta (IL-1B) are proinflammatory cytokine genes at the interleukin-1 locus, and polymorphisms of these genes have been associated with various inflammatory diseases. The aim of this study was to investigate whether polymorphism in the IL-1RN and IL-1B genes are associated with GBC patients with and without gallstones. Polymorphisms within the IL-1RN 86-base pair VNTR (variable number tandem repeat) and IL-1B (-511C --> T) were genotyped using polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism in 166 healthy subjects and 124 GBC patients. The frequency of the IL-1RN, VNTR 2/2 genotype was significantly higher in GBC patients [P = 0.017; odds ratio (OR) = 3.25; 95% confidence interval (CI) = 1.23-8.58]. CC genotype and 'C' allele of the -511IL-1B C --> T polymorphism also showed high risk for GBC (P = 0.033; OR = 3.36; 95%CI = 1.52-7.43, P = 0.047, OR = 1.41; 95%CI = 1.00-1.98, respectively). The higher cancer risk due to the IL-1RN, 2/2 genotype was observed in GBC patients with or without stones (P = 0.038; OR = 3.58; 95%CI = 1.08-11.65, P = 0.035; OR = 3.33; 95%CI = 1.08-10.61). Risk due to the CC genotype of IL-1B, however, was confined to GBC patients harboring gallstones (P = 0.0003; OR = 6.92; 95%CI = 2.65-18.03). The haplotype 1/C of IL-1RN and IL-1B was found to confer a significantly enhanced risk of GBC in cancer patients with gallstones (P = 0.022; OR = 2.19; 95%CI = 1.12-4.27), while higher risk resulting from 2/C haplotype was of borderline significance (P = 0.061; OR = 3.04; 95%CI = 0.95-9.70). Individuals with 1/C and 2/C haplotypes of IL-1RN VNTR and -511IL-1B C --> T polymorphisms were more susceptible to develop GBC with gallstones compared to healthy controls in north India.     

The interleukin 1B-511 polymorphism is associated with the risk of developing restenosis after coronary stenting in Mexican patients

Inflammation is the primary response to vessel wall injury caused by stent placement in coronary arteries. Cytokines of the interleukin-1 family are central regulators in immunoinflammatory mechanisms. The objective of this study was to test for association between IL-1 family gene polymorphisms and risk for restenosis after coronary stent placement. The IL-1B-511, IL-1F10.3, RN.4T>C, RN.6/1C>T, RN.6/2C>G, and IL-1RN VNTR polymorphisms were analyzed by 5' exonuclease TaqMan genotyping assays and polymerase chain reaction in a group of 165 patients who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed in search of angiographic predictors of restenosis and follow-up angiography was analyzed in search of binary restenosis. Patients with IL-1B-511 TT genotype had a 1.89-fold increased risk of developing restenosis. The analysis considering the lesions treated demonstrated that the lesions of patients with IL-1B-511 TT genotype had a 3.44-fold increased risk of developing restenosis. When the analysis considered the type of stent, the risk of developing restenosis was increased in lesions of patients with TT genotype (odds ratio = 4.50) who underwent coronary bare-metal stent implantation. Multiple logistic analysis identified IL-1B-511 TT genotype as an independent predictor for restenosis. The results suggest that IL-1B-511 polymorphism could be involved in the risk of developing restenosis after coronary stent placement.     

Interleukin-1 receptor antagonist and interleukin-1β-511 gene polymorphisms among Egyptian children with febrile seizures

Febrile seizures (FSs) are the most common form of childhood seizures. The higher levels of pro-inflammatory cytokines in children may induce seizures, and alternatively, higher levels of anti-inflammatory cytokines may act as a defense mechanism against seizures. We aimed to investigate whether interleukin (IL)-1β-511 C/T (pro-inflammatory cytokine) (rs16944) and IL-1 receptor antagonist (IL-1Ra) (an anti-inflammatory cytokine) gene polymorphisms could be used as markers for prediction of susceptibility to FSs. The current study included 22 patients with FSs and 22 normal control subjects. All patients were subjected to thorough history taking, full neurological examination, electroencephalography, and peripheral blood sampling for genotype analyses. Detection of IL-1Ra gene polymorphisms was done using polymerase chain reaction (PCR), while a restriction fragment length polymorphism analysis of the PCR products was used for the detection of IL-1β-511 C/T gene polymorphisms. The mean age of onset of first febrile seizures was 15.7 months. Eighteen (81.8 %) cases had the criteria of complex FSs. Frequencies of alleles C and T for IL-1β-511 were 26/44 and 18/44, respectively, in FS patients and 22/44 for both in the control subjects. The CC genotype was significantly more common in the FS patients than in the control group. The IL-1Ra-I homozygote was more frequent in patients with FSs than in healthy controls. The IL-1Ra homozygous I/I and IL-1β-511 CC gene polymorphisms are associated with a higher susceptibility to febrile seizures, which may be useful markers for predicting the development of febrile seizures.     

Association of interleukin-1beta and interleukin-1 receptor antagonist polymorphisms with bacterial vaginosis in non-pregnant Italian women

Bacterial vaginosis (BV) is the most prevalent alteration of vaginal microflora worldwide. BV is a polymicrobial disorder, and its etiology is elusive. Factors predisposing to this recurrent condition are not fully characterized. We aimed to investigate whether interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) polymorphisms are associated with BV in non-pregnant white Italian women. Genomic DNA was obtained from 164 BV positive, and 406 control women. Two diallelic polymorphisms in the IL-1beta gene (IL-1B) representing C/T base transitions at - 511 and + 3954 positions and a variable number tandem repeats (VNTR) in intron 2 of the IL-1ra gene (IL-1RN) were assessed. We demonstrated that women who were homozygous for - 511 CC or + 3954 TT of the IL-1B gene were at increased risk for BV with an odds ratio (OR) = 1.5 [95% confidence interval (CI) = 1.03-2.14, P = 0.032], and OR = 2.8 (95% CI = 1.37-5.88, P = 0.004), respectively. The haplotype - 511/ + 3954 T-C was protective for BV, with an OR = 0.7 (95% CI = 0.49-0.90, P = 0.009). The IL-1RN VNTR genotype was not associated with BV, although the rare allele 3 showed a trend towards protection (P = 0.049). These data show that host genetic variants at the IL-1beta locus predispose to BV among Caucasian non-pregnant women. Further studies will determine whether these genetic polymorphisms modulate the risk for BV recurrence, and/or BV associated severe adverse outcomes as preterm birth and human immunodeficiency virus transmission.     

Lack of association between interleukin-1 alpha,beta polymorphisms and Parkinson's disease

The associations between interleukin-1 alpha (IL-1α-889) and beta (IL-1β-511) single nucleotide polymorphisms (SNPs) and the risk for Parkinson's disease (PD) are still controversial and ambiguous. The aim of this study was to determine a more precise estimation of the relationship by meta-analysis. We searched databases through March 2010 for all publications on the association between these variations and PD. A total of 11 studies including 2803 PD patients and 2539 healthy controls were identified. The overall and geographic subgroups analysis was conducted, and odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in the fixed- or random-effects model. We found that the overall OR (95% CI) for TT and CT genotypes versus CC genotype for IL-1α-889 was 1.01 (0.88–1.16), while the overall OR (95% CI) for TT and CT genotypes versus CC genotype for IL-1β-511 was 1.19 (0.87–1.62). The sensitivity analysis strengthened our confidence in the validity of these null associations. There was no publication bias observed in this study. To sum up, there were no associations found between the SNPs of IL-1α-889, IL-1β-511 and risk for PD.     

C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease.

C-reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)-1beta, IL-1 receptor antagonist and IL-6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(-511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(-174) and IL-6(-572). CRP values were logarithmically normalized (log-CRP) for statistical calculations. In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311-0.574) for CT or TT genotypes compared with 0.240 (0.107-0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l(-1), respectively. Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115-0.388) for carriers and 0.421 (0.290-0.552) for non-carriers (CRP 1.79 and 2.64 mg l(-1), respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2. We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL-1RN(VNTR)*2 with lower CRP levels in the same patients.     

Potential influence of interleukin-1 haplotype IL-1 beta-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: a case-control study

Interleukin (IL)-1 gene polymorphisms affect several inflammatory diseases, including cancer. Therefore, we studied genetic association of biallelic (-511C>T) polymorphism of IL-1β and 86-bp VNTR polymorphism of IL-1RN in 159 patients with esophageal cancer (EC) and 194 age- and gender-matched healthy controls. Genetic analysis for IL-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of IL-1β (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, IL-1β -511TT genotype and T1+ haplotype combination illustrated low risk for disease at the middle third location of the tumor (odds ratio [OR] = 0.27; 95% confidence interval [CI] = 0.11–0.62; p = 0.002; OR = 0.462; 95% CI = 0.253–0.845, p = 0.01). In conclusion, subjects with IL-1β -511TT genotype or IL-1β*T-IL-1RN*1 (T1) haplotype had lower risk for middle third tumor location of EC in a northern Indian population.     

Haplotypes of the IL-1 gene cluster are associated with gastroesophageal reflux disease and Barrett’s esophagus

Objectives

Gastroesophageal reflux (GERD) is a one of the major public health problem that can lead to reflux esophagitis (RE), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC). The aim of our study was to determine the impact of IL-1 gene polymorphisms on the development of GERD, RE and BE.

Methods

Three hundred and thirty-three Czech patients with gastroesophageal reflux and 165 healthy controls were included in this case-control study. Four polymorphisms in the genes of the IL-1 cluster [IL-1A(-889C/T), IL-1B(−511C/T), IL-1B(+3953C/T), and IL-1RN(VNTR)] were analyzed.

Results

Significant differences were found in IL-1RN 1/2 genotype between patients with GERD/RE and controls and in IL-1B+3953 T allele between patients with BE and healthy subjects. In addition, complex analysis revealed differences in IL-1 haplotype frequencies between the groups. Specifically, the haplotype TCCL was significantly more frequent (p = 0.016) in GERD patients than in controls and the haplotype CCCL more frequent (p = 0.008) in RE patients than in controls. However, in patients with BE, frequency of haplotype TCTL was lower (p = 0.05) and haplotypes CTCL and TCCL were higher (p = 0.03 and p = 0.02) in comparison with the controls.

Conclusions

Our results suggest that IL-1 haplotypes may be associated with susceptibility to GERD, RE and BE.