IL4 , IL10 , IL16 , and TNF polymorphisms in New Zealand Caucasian Crohn’s disease patients (original) (raw)
Related papers
Clinical and Experimental Immunology, 2000
Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-a plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair polymorphism located in the promoter region of TNF gene, in a large population of CD patients with well defined phenotypes. One hundred and ninety-three patients with CD and 98 ethnically matched controls were studied. The ¹308 single base pair polymorphism of TNF gene was studied using an allele-specific polymerase chain reaction. Genotype and allelic frequencies were compared between patients and controls and between subgroups of patients defined by sex, age at diagnosis, familial history, location of disease, type of disease, extra-intestinal manifestations, and response to steroid treatment. In 29 patients a measure of TNF-a production by colonic biopsies was performed. The frequency of the allele TNF2 as well as the proportion of carriers of the allele TNF2 were slightly but not significantly lower in CD than in controls (11·9% versus 14·8% and 21·5% versus 27·6%, respectively). A more prominent difference in frequencies of allele TNF2 and in proportions of TNF2 carriers was found when comparing subgroups of patients. The frequency of allele TNF2 was significantly higher in steroid-dependent than in non-steroid-dependent disease (28·1% versus 10·3%; D ¼ 17·8%, 95% confidence interval (CI) ¼ 6·3-29·5%, P ¼ 0·0027) and tended to be higher in colonic than in small bowel disease and in fistulizing than in stricturing disease. Furthermore, TNF2 carriers tended to be more frequent in patients with steroid-dependent than non-steroid-dependent disease (43·8% versus 19·3%; D ¼ 24·5%, 95% CI ¼ 3·6-45·4%, P ¼ 0·022), in patients with fistulizing than stricturing disease (26·5% versus 9·6%; D ¼ 16·9%, 95% CI ¼ 1·1-32·6%, P ¼ 0·036), and in patients with colonic than small bowel disease (26·5% versus 11·1%; D ¼ 15·4%, 95% CI ¼ ¹0·8-31·6%, P ¼ 0·063). Finally, patients carrying at least one copy of allele 2 were found to produce slightly more TNF-a at the colonic level. The ¹308 TNF gene polymorphism may have a slight influence on the behaviour of CD. The carriage of allele 2 may favour steroid-dependent disease and to a lesser extent fistulizing and colonic disease, possibly secondary to a more intense TNF-a-driven inflammatory reaction at the mucosal level.
Clinical and Experimental Immunology, 2007
In 153 patients with IBD, 64 with Crohn's disease (CD), and 89 with ulcerative colitis (UC), as well as in 54 healthy controls (HC), the frequencies of four known di-allelic polymorph isms in the genes for TNF-a and Iymphotoxin alpha (LTa) were investigated. In the Dutch population, the alleles of these four polymorphisms are present in only five combinations, called TNF haplotypes: TNF-C, -E, -H, -I, -Po Furthermore, the relation with the presence of perinuclear anti-neutrophil cytoplasmic autoantibodies (P-ANCA) was studied. A small, but statistically significant, associa tion between the polymorphism at position -308 in the promoter region of the TNF-a gene and UC was found. The frequency of the uncommon TNF-a -308 allele 2 was found to be decreased in patients with UC compared with HC (allele frequency of allele 2 in UC patients O· 15 versus 0·25 in HC, P = 0,044). No significant differences in distribution of the TNF haplotypes were found between IBD patients and HC, although there was a tendency towards a higher frequency of the TNF-C haplotype in UC patients compared with controls (haplotype frequency 22% versus 13%; P = 0'19). No statistically significant differences in distribution of the TNF haplotypes were observed between P-ANCA-positive and P-ANCA-negative UC patients. The strength of the associations indicates that TNF genes are not markers for the predisposition to suffer from IBD. They may, however, be markers of subsets of patients with UC and CD.
Genes & Immunity, 2000
The influence of biallelic polymorphisms in the tumour necrosis factor-alpha (TNF␣), lymphotoxin-alpha (LT␣) and interleukin-10 (IL-10) genes on stimulated TNF␣ and IL-10 production was studied in ulcerative colitis (UC) patients, Crohn's disease (CD) patients and in healthy controls. A polymerase chain reaction sequence-specific primer (PCR-SSP) system was developed to type nine biallelic polymorphisms, three in each of the TNF␣, LT␣ and IL-10 genes. Production of the TNF␣ and IL-10 was measured by ELISA in lipopolysaccharide (LPS) stimulated whole blood. Four haplotypes of the TNF␣ gene, three haplotypes of LT␣ and three haplotypes of IL-10 were identified. No significant differences in haplotype frequencies were found between patients and controls overall. On subgroup analysis however, haplotype TNF-2 was more frequent in women with extensive colitis compared to distal colitis (31% vs 12%; P = 0.028). This difference was even greater for the combined TNF-2-LT␣-2 haplotype (56% vs 21%; P = 0.0007). The TNF-2 and LT␣-2 haplotypes were associated with higher TNF␣ production in CD patients, and the TNF-4 haplotype was associated with lower TNF␣ production in UC patients. The A allele in the IL-10 promoter region at position −1082 was associated with decreased IL-10 production in CD patients and controls (P = 0.005, P = 0.015 respectively). These data provide evidence that the effect of TNF␣, LT␣ and IL-10 gene polymorphisms on cytokine production differ in CD, UC patients and controls. Genes and Immunity (2000) 1, 185-190.
Middle East journal of digestive diseases, 2014
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, relapsing, inflammatory disorder of the gastrointestinal tract that includes two entities, Crohn's disease (CD) and ulcerative colitis (UC). As with other complex diseases, both genetic susceptibility and environmental factors play role in the pathogenesis of these diseases. The tumor necrosis factor α (TNF-α) gene is located in the IBD3 region on chromosome 6p21 which is a good functional candidate for involvement in susceptibility to IBD. In addition, the promoter region of TNF-α contains various polymorphisms that have shown a significant association with IBD. METHODS In this case control study we investigated the TNF-α -857 polymorphism in 109 patients (89 UC and 16 CD) who suffered from IBD and 100 healthy age, sex and ethnicity matched adults selected from the same population, as the control group. The polymorphism was checked by amplification refractory system (ARMS) and polymerase chain reaction (PCR). RESULTS Inv...
Journal of Inflammation Research, 2016
Inflammatory bowel disease (IBD) is a complex, multifactorial, chronic inflammatory disorder of the gastrointestinal tract in which immune dysregulation caused by genetic and/or environmental factors plays an important role. The aim of this casecontrol study was to evaluate the association of tumor necrosis factor-alpha (TNF-α) (308) and-β (+252) polymorphisms with susceptibility of IBD. A total of 379 Saudi subjects including 179 IBD patients (ulcerative colitis (UC) =84 and Crohn's disease (CD) =95) and 200 age-and sex-matched healthy controls were recruited. TNF-a and TNF-b genes were amplified using an amplification refractory mutation systems polymerase chain reaction methodology to detect TNF-α (-308) and-β (+252) polymorphisms. The frequency of the GA genotype of TNF-α (-308G/A) was higher, and the frequencies of the GG and AA genotypes were significantly lower in IBD patients compared with those in controls, indicating that genotype GA-positive individuals are susceptible to IBD and that the GG and AA genotypes exert a protective effect. The frequency of allele A of TNF-α (-308G/A) was significantly higher and that of allele G was lower in IBD patients compared with those in controls, indicating an association of allele A with IBD risk in Saudi patients. On stratification of IBD patients into UC and CD, an almost similar pattern was noticed in both the groups. The results of TNF-β (+252A/G) polymorphisms showed a significant increase in the frequency of the GG genotype in IBD patients, suggesting a positive association of GG genotype with IBD risk. On stratification of IBD patients into UC and CD, the genotype GG of TNF-β was associated with susceptibility risk to UC but not CD. The frequencies of alleles and genotypes of both TNF-α and-β polymorphisms are not affected by sex or type of IBD (familial or sporadic). TNF-α (-308G/A) and TNF-β (+252A/G) polymorphisms are associated with risk of developing IBD in Saudi population.
Cytokine gene polymorphisms in inflammatory bowel disease
Gut, 1996
Background-Concordance rates in siblings and twins provide strong evidence that genetic susceptibility is important in the pathogenesis of inflammatory bowel disease. The number and identity of susceptibility genes is largely uncertain. Cytokine genes are attractive candidate loci. Aims-To study allelic frequencies of polymorphisms of the interleukin-1 receptor antagonist (IL-1RA) gene and the tumour necrosis factor ae gene in patients with inflammatory bowel disease. Subjects-One hundred and twenty nine North European caucasoid patients with ulcerative colitis, 120 patients with Crohn's disease, and 89 healthy controls. Methods-Genotyping was performed by polymerase chain reaction. A variable number of tandem repeats (VNTR) in the IL-1RA gene and a single base pair polymorphism in the TNFa gene promoter region (TNF-308) were analysed. Results-No significant differences in IL-1RA VNTR allelic frequencies were noted between Crohn's disease (allele 1: 72.6%, allele 2: 24.7%, allele 3: 2.6%), ulcerative colitis (72.6%, 24.3%, 3.1%, respectively), and controls (76.9%, 20.8% and 2.3%). Some 42.4% of patients with ulcerative colitis and 43.4% patients with Crohn's disease were carriers of allele 2, compared with 34.8% healthy subjects. The TNF2 allele was modestly reduced in Crohn's disease (13.2%), compared with healthy subjects (21.3%; p=0.04), and ulcerative colitis (21.6%). Conclusions-The associations demonstrated are modest: these polymorphisms are unlikely to be important determinants of overall disease susceptbility.
Journal of Gastrointestinal Cancer, 2011
Objective Inflammatory bowel diseases (IBDs), namely ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic and idiopathic inflammatory conditions of gastrointestinal tract that are immunologically mediated. Single nucleotide polymorphisms in cytokine genes have been reported to modulate inflammation. Therefore, we analyzed the association of pro/ anti-inflammatory cytokine genes polymorphism with IBD susceptibility. Methods Genotyping of interleukin (IL)-4 repeat polymorphism in intron-3, IL-10 (G-1082A and C-819T), and tumor necrosis factor-alpha (TNF-A) (−1031 T>C, −863 C>A, and −857 C>T) was performed in 153 patients with IBD and in 207 controls. Results TNF-A −863 AA genotype was associated with enhanced IBD susceptibility (odds ratio (OR), 4.82; 95% confidence interval (CI), 2.60-8.96), more so for UC (OR, 5.79; 95% CI, 2.99-11.21), Crohn's disease [CD] (OR, 3.13; 95% CI, 1.16-8.47). TNF-A T/C/T (OR, 4.40; 95% CI, 1.64-11.81) and C/A/C (OR, 4.15; 95% CI, 2.48-6.96) haplotypes were associated with increased IBD risk. The frequency of IL-4, B2 carrier (B1/B2+B2/B2) was significantly lower in left-sided UC (17.1%) than proctosigmoiditis (47.6%); p, 0.016. In contrast, TNF-A −863 AA genotype frequency was much higher in pancolitis (45.5) than in proctosigmoiditis (14.2); p, 0.037. Variant genotypes of IL-4 (B1/B2+B2/B2) were absent in colonic type CD. IL-10 polymorphisms did not demonstrate any association with IBD. None of the polymorphisms were associated with steroid treatment and surgery. Conclusion The present study depicts that high-producing genotype of TNF-A (−863 AA) was associated with increased risk of IBD more so with UC. Similarly, combined effect of TNF-A polymorphisms in haplotype analysis demonstrated additively increased risk of IBD.