IL-10 and IL-6 gene polymorphisms as potential host susceptibility factors in Brucellosis

Several genes encoding for different cytokines may play crucial roles in host susceptibility to Brucellosis, since the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphism. The association of the cytokine gene polymorphisms with the development of Brucellosis was investigated in this study. DNA samples were obtained from a Turkish population of 40 patients with Brucellosis, and 50 healthy control subjects. All genotyping (IL-6, IL10, IFN-gamma, TGF-beta and TNF-alpha) experiments were performed using sequence-specific primers PCR (PCR-SSP). When compared to the healthy controls, the frequencies of high/intermediate producing genotypes of IL-10 and high producing genotype of IL-6 were significantly more common in the patient group. These results suggest that IL-10 and IL-6 gene polymorphisms may affect susceptibility to Brucellosis and increase risk of developing the disease. In order to confirm the biological significance of our results, further studies should be performed in larger population groups.     

Interleukin-10 (IL-10) gene polymorphism as a potential host susceptibility factor in tuberculosis

Several genes encoding for different cytokines may play crucial roles in host susceptibility to tuberculosis (TB), since the cytokine production capacity varies among individuals and depends on the cytokine gene polymorphism. The association of the cytokine gene polymorphisms with the development of TB was investigated in this study. DNA samples were obtained from a Turkish population of 81 patients with the different clinical forms of TB, and 50 healthy control subjects. All genotyping (IL-6, IL-10, IFN-gamma, TGF-beta and TNF-alpha) experiments were performed using sequence-specific primers PCR (PCR-SSP). Analysis of allele frequencies showed that IL-10 -1082 G allele frequency was significantly more common in TB patients than healthy controls (37.7% vs 23.0%, p: 0.014). No statistically significant differences were observed between the different clinical forms of the disease. These results suggest that the polymorphisms in IL-10 gene may affect susceptibility to TB and increase risk of developing the disease. To confirm the biological significance of our results, further studies should be performed on other population groups.     

TGF-beta1 and IL-6 gene polymorphism in Spanish brucellosis patients

Polymorphisms in the cytokine genes have allowed for the understanding of the genetic determinants in several diseases. We investigated the polymorphism of the transforming growth factor (TGF)-beta1 and IL-6 genes in relation to susceptibility to human brucellosis. We typed 82 Spanish brucellosis patients and 102 healthy controls for TGF-beta1 polymorphisms in codons 10 and 25, and IL-6 promoter polymorphism at position -174 by PCR-SSP methods. The T/T G/G genotype of the TGF-beta1 gene was significantly increased in patients compared to controls (49% vs. 32%) P=0.02; OR=1.99 (1.05-3.80) and the T/C G/G genotype was significantly less common in the patients compared to the controls (32% vs. 49%) P=0.01; OR=0.48 (0.25-0.92). The CC genotype of codon 10 was significantly increased in the patients who had focal forms of the disease as compared with those who did not develop focal forms (19% vs. 4%), P=0.03; OR=0.19 (0.02-1.10). No differences were found in the IL-6 variants between the patients and the controls. These results suggest that polymorphism of the TGF-beta1 gene may be involved in susceptibility to brucellosis and to developing focal forms of the disease in a group of patients from southern Spain.     

Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis

BACKGROUND: Several genes coding for different cytokines may affect host susceptibility to tuberculosis. METHODS: In the present study, the allele and genotype frequencies of a number polymorphic genes coding for cytokines or cytokine receptors were investigated in Iranian patients with pulmonary tuberculosis (PTB). RESULTS: From the IL-1 cluster, a positive, significant difference was found at position -889, where the T/T genotype was over represented in PTB patients (p = 0.01); a positive, significant increase was found in the IL1R PstI 1970 C/C genotype, where the C allele was over represented in the PTB patients (p = 0.01). A significant negative association at codon 10 TGF-beta, T allele, was shown in our patients and the C allele and C/C genotype were over represented in the PTB patients (P<0.005). For TNF-alpha at position -238, we found a negative association for the G/A genotype and a positive association for the G/G genotype (p = 0.0009). Significant negative associations at position -590 IL-4, T allele and the T/T genotype were shown in our patients (p = 0.0007); also, the C allele and T/C genotype were significantly increased in our patients (P<0.05). With IL-6 at -174, G/G increased and G/C decreased significantly in the patients (P<0.005). CONCLUSION: Pro-inflammatory cytokines such as TNF-alpha and TGF-beta seem to be decreased, and IL-6 increased in PTB patients.     

Relevance of transforming growth factor-beta1, interleukin-8, and tumor necrosis factor-alpha polymorphisms in patients with chronic pancreatitis

Cytokine regulation may be an important factor in the susceptibility for the development of chronic pancreatitis; transforming growth factor-beta1 (TGF-beta1) plays a central role in the pathogenesis of pancreatic fibrogenesis. The aim of our study was to analyse the relevance of TGF-beta1, interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) polymorphisms in patients with chronic pancreatitis. PATIENTS: of the 83 patients enrolled in the study, 43 were treated medically and 40 patients underwent surgical intervention. Healthy blood donors (n=75) served as controls. METHODS: the polymorphisms of TGF-beta1 +869 T--> C and IL-8 -251 T-->A were determined by the ARMS method, while that of TNF-alpha -308 was investigated using NcoI RFLP. RESULTS: there was a higher frequency (50%) of the TT genotype of TGF-beta1 +869, with a concomitantly higher TGF-beta1 level in the plasma (5.2 +/- 1.7 ng/mL) of patients with chronic pancreatitis than in healthy blood donors (28% and 2.8 +/- 0.9 ng/mL respectively). The number of TT homozygotes differed significantly between the patients who underwent surgical intervention and the controls, and even between the surgical and the non-surgical patients. The frequency of the T/A genotype with higher IL-8 production, was significantly higher in both groups of patients than in the controls (58% and 58% versus 40%). No correlation was found between the TNF-alpha -308 polymorphism and chronic pancreatitis. CONCLUSIONS: correlations of the TGF-beta1 and IL-8 single nucleotide polymorphisms (SNPs) with chronic pancreatitis underline the importance of these cytokines in the pathomechanism of the disease. Moreover, it seems that the TT genotype of +869 TGF-beta1 might be a risk factor for the development of a severe form of chronic pancreatitis, and could serve as a prognostic sign for any future surgical intervention or even repeat surgery. Further studies on a larger group of patients, in addition to a follow-up study, are necessary to confirm this preliminary observation.     

Cytokine single nucleotide polymorphisms in Iranian populations

Cytokines are important immunomodulatory molecules involved in immune responses against microorganisms; they also have an important role in the setting of immune system disorders. Cytokine single nucleotide polymorphisms have been extensively studied in different, normal populations as well as in association with disease. Cytokine gene polymorphisms are potentially important as genetic predictors of disease susceptibility, clinical outcome, and as a tool for anthropological studies. In this study, samples have been collected from 455 healthy individuals located in different regions of Iran (Tehran, Yazd, Sistan and Balochistan). Allele and genotype frequencies of cytokine SNP, including: IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-4RA, IL-6, IL-10, IL-12, TNF-alpha, TGF-beta and IFN-gamma were investigated, using the PCR-SSP method. Allele frequencies in Tehran and Yazd populations were similar, except for TGF-beta. Allele frequencies in Sistani & Baloch populations were similar at all positions, except for IL-1beta at position of -511 and IFN-gamma genes at position UTR5644; there were some differences in allele frequencies comparing these populations with the Yazd population, including: IL-4, IL-6, IL-10, TGF-beta and TNF-alpha. Although some significant differences were observed for some cytokines, it seems that the cytokine gene polymorphism profile of the Iranian population is similar to that of Caucasians, particularly the Italian population.     

Interleukin-4 -590T/C polymorphism influences the susceptibility to nonsmall cell lung cancer

Lung cancer is the leading cause of cancer mortality worldwide. Nonsmall cell lung cancer (NSCLC) accounts for most of these cases. Interleukin 4 (IL-4) is a typical pleiotropic T helper 2 cytokine and plays crucial roles in tumor immunology. IL-4 gene -590T/C polymorphism has been shown to be associated with different autoimmune diseases and cancers. The present study evaluated the correlation between this polymorphism and the susceptibility to NSCLC in the Chinese population. The IL-4 variant -590T/C was detected by polymerase chain reaction-restriction fragment length polymorphism in 1072 NSCLC cases and 1126 age-matched healthy controls. Data were analyzed using the Chi-square test. Results showed that frequencies of IL-4 -590 TC, CC genotype, and -590 C allele were significantly lower in patients with NSCLC than in healthy controls (odds ratio [OR]=0.77, 95% confidence interval [CI] 0.64-0.93, p=0.006; OR=0.54, 95% CI 0.38-0.76, p=0.0004; and OR=0.72, 95% CI 0.62-0.83, p=1.1 × 10(-5), respectively). Our data suggest that the -590T/C polymorphism of the IL-4 gene is associated with a decreased susceptibility to NSCLC.     

Genetic polymorphism of interleukin-8 (IL-8) is associated with Helicobacter pylori-induced duodenal ulcer

BACKGROUND AND AIMS: Helicobacter pylori infection almost invariably causes chronic gastritis, but only a proportion of the infected subjects develop peptic ulcers. The local inflammation associated with H. pylori infection is characterized by an increased production of the proinflammatory cytokines IL-1-B, IL-6, IL-8 and TNF-alpha. Since such cytokine production is often determined by the genetic polymorphism of regions regulating cytokine gene expression, we investigated the relationship between TNF-alpha and IL-8 polymorphisms and the development of duodenal ulcer disease. We also sought a correlation between the promoter polymorphism of the lipopolysaccharide (LPS) receptor CD14 and the formation of peptic ulcer, because CD14 plays a crucial role in the initiation of the cytokine cascade. METHODS: Genomic DNA extracted from the peripheral blood of 69 patients with H. pylori-positive duodenal ulcer disease and 47 H. pylori-positive healthy controls was analyzed for TNF-alpha -308 promoter polymorphism by RFLP, and for IL-8 -251 polymorphism by ARMS. Genetic polymorphism within the promoter of the CD14 gene was identified using the LightCycler instrument via melting point analysis. RESULTS: No significant correlation could be revealed between the TNF-alpha and CD14 promoter polymorphisms and the clinical outcome of H. pylori infection. The IL-8 A/T heterozygote mutant variant was detected with a significantly higher frequency (65.22%) among the ulcer patients than among the healthy, H. pylori-positive blood donors (36.17%), while the frequency of the normal allelic genotype (TT) was significantly higher in the control group (44.6% vs 15.9%). CONCLUSION: Analysis of the genetic predisposition to enhanced cytokine production revealed a significant association only for the IL-8 polymorphism. This observation draws attention to the possible importance of IL-8 polymorphism as a genetic predisposing factor in the pathomechanism of H. pylori-induced duodenal ulcer disease, and to the relative protection from duodenal ulcer disease that is associated with the TT genotype.     

Polymorphisms of IL-10 gene in patients infected with HCV under antiviral treatment in southern Brazil

Interleukin-10 (IL-10) is a cytokine that plays an important role in the regulation of the immune system. Gene polymorphisms of IL-10 have been associated with the different expression levels of this cytokine. In hepatitis C virus infection, IL-10 appears to interfere with the progression of disease, viral persistence and the response to therapy. This study investigated genetic variability in the IL-10 gene promoter between patients infected with hepatitis C virus (HCV) and healthy individuals, associating the frequency of polymorphisms with different aspects of viral infection. This is a case-control study with 260 patients who were infected with HCV and 260 healthy individuals. Genotyping of the polymorphisms was performed using the technique of amplification refractory mutation system PCR (ARMS-PCR) for regions of the IL-10 gene promoter (-1082 G/A, -819 C/T, -592 C/A). The frequencies of alleles and genotypes related to polymorphisms in the IL-10 gene promoter showed a higher frequency of the G allele and genotype GG in the -1082 region between the infected group and the control group (p = 0.005 and p = 0.001, respectively), whereas the AA genotype was significantly more frequent in the control group. The frequencies of the haplotypes GTA and GCC were higher in the group of infected individuals, whereas the haplotype ATA was more frequent in the healthy group (p < 0.006). It was also observed that the genotypes GG and AG in the region -1082 were significantly more frequent among patients infected with HCV who were in advanced stages of fibrosis and cirrhosis (p = 0.042). No association was observed between polymorphisms of IL-10 and sustained virologic response (SVR).     

Association of IL-12, IL-18 variants and serum IL-18 with bladder cancer susceptibility in North Indian population

IL-12 and IL-18 are immunomodulatory cytokines that play important roles in host immune response against cancers. Variation in DNA sequence in gene promoter may lead to altered IL-18 production and/or activity, and hence can modulate an individual's susceptibility to BC. To test this hypothesis, we investigated the relationship of IL-18 gene promoter −137 G/C and −607C/A polymorphisms and IL12 (− 16974) A/C with the risk of BC in North Indian population. Polymorphisms in IL-18 and IL-12 genes were analyzed in 200 BC patients and 200 age, ethnicity and sex-matched controls, using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP) and amplification refractory mutation specific-polymerase chain reaction (ARMS) method. The concentrations of IL-18 in serum were determined by ELISA. Significant association was observed with IL18 (− 137) G/C heterozygous genotype (GC) with 1.96 folds risk of BC as well at C allele carrier and variant C allele having 2 fold and 1.6 fold risk for BC respectively. IL18 (− 607) C/A, heterozygous CA genotype also showed a high risk (OR = 1.59) for BC. While IL12 (− 16974) A/C heterozygote genotype and C allele carrier demonstrated reduced risk of BC. Hetero genotype of IL18 (− 137) G/C was associated with risk of recurrence (HR = 2.35) in superficial BC patients receiving BCG treatment thus showing least survival. The distributions of IL-18 gene haplotypes were not significantly different between patients and controls. Serum IL-18 levels were significantly higher in BC patients than in the healthy subjects (p = 0.025). Serum IL-18 levels was also significantly associated with IL18 (− 137) G/C in heterozygous genotype (GC) (p = 0.048). Our results suggest that IL-18 gene polymorphism contributes to bladder cancer risk whereas IL-12 is protective. A relation between IL18 (− 137) G/C in heterozygous genotype with elevated IL-18 serum level and bladder cancer risk has been registered in the present study.     

Influence of the -308 TNF-alpha and -174 IL-6 polymorphisms on lipid profile in Mexican subjects

Polymorphisms in the promoter region of several cytokine genes have been associated with differential cytokine production. Several reports indicate that polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) genes are associated with lipid abnormalities. The aim of this study was to identify the genotype frequencies for -308G/ATNF-alpha and -174G/CIL-6 polymorphisms in Mexican subjects and to determine the influence of both polymorphisms on serum lipid levels. Serum lipid concentrations were measured in 100 healthy Mexican subjects. Screening of the -308G/ATNF-alpha and -174G/CIL-6 polymorphisms was performed in all participants using PCR-RFLPs. Genotype frequency for TNF-alpha polymorphism was: 87% GG and 13% GA, whereas IL-6 polymorphism was: 77% GG and 23% GC. The polymorphism frequencies obtained in this study were significantly different to Caucasian populations. High serum levels of triglycerides and total cholesterol were associated with GG genotype of the -308 TNF-alpha polymorphism, as well as low HDL-c levels, but no association was found between the -174 IL-6 polymorphism and serum lipid concentrations. We observed a significant association of the -308 TNF-alpha polymorphism with lipid profile in Mexican subjects. Furthermore, the genotype distribution of -308 TNF-alpha and -174 IL-6 polymorphisms in Mexican Mestizo population similar to populations in different continents may be due to our genetic background influenced by the mixture of Spaniards, Indian and black genes.     

Association between IL-27 2905T/G genotypes and the risk and survival of cervical cancer: a case-control study

Background: Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties.

Patients and methods: A case-control study was conducted to investigate the possible associations of IL-27 gene polymorphisms with susceptibility to cervical cancer and clinical outcome.

Results: Our results suggested that the IL-27 2905T/G was significantly associated with a decreased risk of cervical cancer. Further analysis showed IL-27 2905T/G genotypes were associated with advanced tumor stages of cervical cancer patients. More interestingly, the IL-27 2905T/G genotypes were statistically significantly associated with the survival in cervical cancer patients.

Conclusion: Our results showed that the IL-27 2905T/G genotypes were associated with decreased the susceptibility and development of cervical cancer in Chinese Han population.     

The lL-8 and IL-13 gene polymorphisms in inflammatory bowel disease and colorectal cancer

Inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are disorders that originate from immune disturbances. In our study, we evaluated the association between the -251 T/A interleukin (IL)-8 and the -1112 C/T IL-13 polymorphisms, the risk of IBD, and CRC development. Genotypes were determined by PCR-restriction fragment length polymorphism in 191 patients with CRC, 150 subjects with IBD, and 205 healthy controls. We found an association between CRC and the presence of the -251 TA genotype and A allele of the IL-8 gene (odds ratios [ORs] 2.28 and 1.65). A similar relationship was observed between these polymorphic variants and ulcerative colitis (OR 2.05 for the -251 TA genotype and OR 1.47 for the -251 A allele) as well as Crohn's disease (ORs 3.11 and 1.56, respectively). Our research also revealed that the CT and TT genotypes of the IL-13 -1112 C/T polymorphism may be connected with a higher risk of CRC (ORs 2.28 and 1.65). The same genotypes affected the susceptibility of IBD (ORs 2.26 and 3.72). Our data showed that the IL-8 -251 T/A and IL-13 -1112 C/T polymorphisms might be associated with the IBD and CRC occurrence and might be used as predictive factors of these diseases in a Polish population.     

The CD14-260 C --> T promoter polymorphism co-segregates with the tumor necrosis factor-alpha (TNF-alpha)-308 G --> A polymorphism and is associated with the interleukin-1 beta (IL-1 beta) synthesis capacity of human leukocytes

Genetic variations contribute to the interindividual variance in the cytokine response to endotoxin. The gene of tumor necrosis factor-alpha (TNF-alpha) carries a polymorphism at position -308 of the promoter, consisting of a G/A exchange. To further elucidate the inherited mechanisms influencing cytokine levels, healthy human blood donors were studied. Genotyping for the TNF-alpha -308 and the CD14 -260 C/T promoter polymorphisms was carried out by real-time polymerase chain reaction assay using specific fluorescence-labelled hybridisation probes. A human whole blood assay was used to study the leukocyte TNF-alpha and IL-1 beta synthesis capacity upon endotoxin stimulation. We found a linkage disequilibrium between the TNF-alpha -308 G/A and the CD14 -260 C/T polymorphisms (p = 0.043). The CD14 -260 polymorphism was associated with IL-1 beta levels (p = 0.033) and higher values were found in C homozygotes. No association was found between the CD14 -260 genotypes or the TNF-alpha -308 - CD14 -260 genotypes and the TNF-alpha response.     

Influence of Atg5 Mutation in SLE Depends on Functional IL-10 Genotype

Increasing evidence supports the involvement of autophagy in the etiopathology of autoimmune diseases. Despite the identification of autophagy-related protein (Atg)-5 as one of the susceptibility loci in systemic Lupus erythematosus (SLE), the consequences of the carriage of these mutations for patients remain unclear. The present work analyzed the association of Atg5 rs573775 single nucleotide polymorphism (SNP) with SLE susceptibility, IFNα, TNFα and IL-10 serum levels, and clinical features, in 115 patients and 170 healthy individuals. Patients who where carriers of the rs573775 T* minor allele presented lower IFNα levels than those with the wild genotype, whereas the opposite result was detected for IL-10. Thus, since IL-10 production was regulated by rs1800896 polymorphisms, we evaluated the effect of this Atg5 mutation in genetically high and low IL-10 producers. Interestingly, we found that the rs573775 T* allele was a risk factor for SLE in carriers of the high IL-10 producer genotype, but not among genetically low producers. Moreover, IL-10 genotype influences SLE features in patients presenting the Atg5 mutated allele. Specifically, carriage of the rs573775 T* allele led to IL-10 upregulation, reduced IFNα and TNFα production and a low frequency of cytopenia in patients with the high IL-10 producer genotype, whereas patients with the same Atg5 allele that were low IL-10 producers presented reduced amounts of all these cytokines, had a lower prevalence of anti-dsDNA antibodies and the latest onset age. In conclusion, the Atg5 rs573775 T* allele seems to influence SLE susceptibility, cytokine production and disease features depending on other factors such as functional IL-10 genotype.     

Interleukin-8 and -10 gene polymorphisms in irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diagnoses seen by primary care providers and gastroenterologists. Proinflammatory cytokines interleukin (IL)-6 and IL-8 have been found increased in IBS patients. Cytokine gene single nucleotide polymorphisms (SNPs) of IL-8 and IL-10 have not been assessed in Mexican IBS patients. DNA was extracted from peripheral blood leucocytes of 45 IBS unrelated patients and 137 controls. Allele, genotype, and haplotype frequencies were determined by analyzing SNPs of IL-8 and IL-10 genes. IL-8 + 396 G allele (P = 0.02), IL-8 + 396(G/G) and IL-8 + 781(C/T) genotypes (P < 0.001), IL-10 - 1082A allele and IL-10 - 1082(A/A) genotype (P < 0.001) were significantly increased in the IBS group. Haplotypes IL-8 ATCC (P = 0.03) and IL-10 ACC (P < 0.001) were associated with susceptibility to develop IBS. An association of certain polymorphisms of IL-8 and IL-10 in IBS patients compared to controls was demonstrated, suggesting a role of these cytokine SNPs in the pathophysiology of IBS.     

Alleles distribution of polymorphic promoter region C-590T in interleukin-4 genes and Q-576r and Ile-50Val regions in IL-4 receptor gene IL-4RA in patients with HCV-infection

81 patients with confirmed HCV-infection and 48 healthy volunteers were examined. In healthy Caucasian participants living in Siberian region significant predominance of C/T genotype in promoter region C-590T of interleukin-4 (IL-4) gene and Q/Q and Ile/Val genotypes in points -50 and -576 of IL-4RA gene that codes alpha-chains of IL-4 receptor were revealed. In patients with HCV-infection predominance of C/T genotype in C-590T region in IL-4 gene (OR = 1.86), R/R genotype in Q-576R region of IL-4RA gene (OR=7.86), and Val/Val genotype in point Ile-50Val (OR = 2.6) of the same gene. Summary predictive coefficient of hepatitis C development in carriers of these genotypes approached to 95%. During analysis of role of allelic polymorphism of IL-4 genes in predisposition to hepatitis C development it is necessary to consider not only presence of allelic variants of promoter regions of the IL-4 genes, but also the polymorphism of genes coding molecules binding with this cytokine on target cells membranes and in its soluble form.     

Genetic polymorphisms in patients with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a family of clonal disorders characterized by dyshematopoiesis and susceptibility to acute myelogenous leukemia. Tumor necrosis factor-a (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the pathogenesis of MDS. There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta protein, and in the -308 promoter region of TNF-alpha. The association between TNF-alpha and TGF-beta1 gene polymorphism and the susceptibility to MDS and the progression of the disease was investigated. As compared with healthy control subjects (n = 74), patients with MDS (n = 55) showed no significant deviations in genotype or allele frequencies of TNF-alpha. Similarly, there were no differences in the distribution of TNF-alpha genotypes between the MDS patients with only anemia (mild group) and those with bi- or pancytopenia (severe group). On the other hand the TT homozygosity at codon 10 in exon 1 of TGF-beta1 gene was associated with a severe degree of cytopenia [95% CI OR = 4.889, p = 0.0071]. These findings suggest that the investigated genetic polymorphisms do not predispose to the development of MDS, but that TGF-beta1 gene polymorphism may affect the disease progression.     

白介素-10-819 C/C和肿瘤坏死因子-α-1031 C/C/基因型与胃十二指肠疾病易感性的关系

目的分析人群中IL-10-819 C/C和TNF-α-1031 C/C基因型与胃十二指肠疾病的关系,确定携带以上该基因型的的人群罹患胃十二指肠疾病易感性的风险性。为临床诊断和预防这些疾病提供新的思路和方法。方法选取H.pylori阳性的48例慢性胃炎患者,46例十二指肠溃疡患者,51例胃溃疡患者,43例胃癌患者和100例健康对照者,2种基因型分别采用普通PCR和多重引物特异PCR法检测。结果在胃炎组中TNF-A-1031各基因型的频率(T/T,50%;T/C,40%;C/C,10%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.975,P0.05)。在胃溃疡组中TNF-A-1031各基因型的频率(T/T,49%;T/C,43%;C/C,8%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.464,P0.001)。在十二指肠溃疡组中TNF-A-1031各基因型的频率(T/T,72%;T/C,26%;C/C,2%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.840,P0.05)。在胃癌组中TNF-A-1031各基因型的频率(T/T,50%;T/C,41%;C/C,9%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.335,P0.001);Logistic回归分析与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生胃炎的危险性为OR=7.60(95%CI:1.38-41.77);与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生胃溃疡的危险性为OR=5.84(95%CI:1.00-33.84);与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生十二指肠溃疡的危险性为OR=7.94(95%CI:1.44-43.67);与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生胃癌的危险性为OR=6.95(95%CI:1.19-40.63)。在疾病组和对照组中IL-10-819的各基因型频率的分布差异无统计学意义(P0.05)。结论 TNF-α-1031基因多态性与胃炎、胃溃疡、十二指肠、胃癌的易感性相关。     

IL-1RN +2018T>C polymorphism is correlated with colorectal cancer

Epidemiological and experimental evidence indicates chronic inflammation as a risk factor for colorectal cancer. We investigated whether IL-1B ?511C>T (rs16944), IL-1B +3954C>T (rs1143634) and IL1-RN +2018T>C (rs419598) cytokine polymorphisms are correlated with colorectal cancer. Blood samples were obtained from 377 Romanian subjects: 144 patients with sporadic colorectal cancer and 233 healthy controls. Polymorphisms were analyzed by allelic discrimination TaqMan PCR assays with specific probes. The results of our study showed that IL-1RN +2018T>C polymorphism is associated with colorectal cancer. We found that there was a significant difference in the frequency of CC genotype between patients with colorectal cancer and the control group (OR 2.42, 95 % CI: 1.06–5.53, p = 0,034) when TT genotype was used as reference. Furthermore, in a stratified analysis, a positive association was found only for IL-1RN +2018CC genotype, that was limited to early I and II stages (OR 2.72, 95 % CI: 1.05–7.03, p = 0,033). We did not find any association between any of the IL-1B polymorphisms and colorectal cancer. In conclusion this study found that IL-1RN +2018T>C polymorphism is associated with colorectal cancer, mainly for localized disease.