A Polymorphism in the TNF-alpha Promoter Gene is Associated with Pediatric Onset and Colonic Location of Crohn's Disease

Levine, Arie; Karban, Amir; Eliakim, Rami; Shaoul, Ron; Reif, Shimon; Pacht, Avi; Wardi, Joram; Yakir, Benjamin; Silver, Esther Leshinsky

doi:10.1111/j.1572-0241.2005.41126.x

Cited by 42 publications

(32 citation statements)

References 39 publications

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“…Mutations of the TNF-␣ promoter gene were analyzed by pyrosequencing technology (35). Polymerase chain reaction was performed in a 50 L volume containing 10 mM tris-HCl, pH 8.3, 50 mM KCl, 1.5 mM MgCl 2 , 250 M dNTPs, 1 M of each primer, 200 ng of genomic DNA and 1.25U of AmpiTaq Gold DNA polymerase (Perkin Elmer Applied Biosystem) with an initial denaturation step of 10min at 95°C to activate the polymerase followed by 35 cycles of 94°C; 15 s, 60°C; 45 s, 72°C; 45 s and final elongation of 10 min at 72°C.…”

Section: Methodsmentioning

confidence: 99%

“…Polymorphisms that have been reported to increase (308G/A) or decrease circulating TNF-␣ (238G/A, 857 C/T, 863 C/A) (27)(28)(29)(30)(31)(32)(33), as well as playing a possible role in disease phenotype and susceptibility (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). The 857C/T and 863C/A polymorphisms appear to be located at transcription factor binding sites (32,34,35).…”

mentioning

confidence: 99%

“…The 857C/T and 863C/A polymorphisms appear to be located at transcription factor binding sites (32,34,35).…”

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confidence: 99%

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Polymorphisms in the TNF-α Promoter and Variability in the Granulomatous Response in Patients with Crohn's Disease

et al. 2006

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Polymorphisms in the TNF-α Promoter and Variability in the Granulomatous Response in Patients with Crohn's Disease

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“…Vatay et al [29] also showed an increased risk in their study on Hungarian subjects. However, several negative studies have been published, including Levine et al [48] who examined a pediatric Jewish population, and Sashio et al [28] in a study on Japanese patients. In particular, the latter authors found a difference in the carrier frequency for haplotype AG (-308 A, -238 Japanese 217 Vatay [29] Hungarian 188 Kim [30] Korean 291 Celik [33] Turkish 225 Yamamoto-Mexican 179 Furusho [34] Current study NZ 820…”

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Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

Ferguson¹,

Hüebner²,

Petermann³

et al. 2008

WJG

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4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ 2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ 2 = 4.86, P = 0.028). CONCLUSION:TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco-or nutrigenomic approaches may be desirable for individuals with such affected genotypes. INTRODUCTIONInflammatory bowel diseases (IBDs) are chronic multifactorial disorders, commonly classified as autoimmune diseases, and comprise of Crohn's disease (CD) and ulcerative colitis (UC). Up to 10%-15% of reported cases are described as "indeterminate colitis" (IC), where an unequivocal classification is not possible using established diagnostic criteria. Twin studies and segregation analysis strongly support IBD, especially CD, as complex genetic traits [1] , whose etiology also involves immunological and environmental factors, including diet. Several IBDsusceptibility chromosomal regions have been replicated Abstract AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a Taqman R assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ 2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ 2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ 2 = in a number of studies, and in some cases causative genes have been found. For example, the key gene in the IBD1 region on chromosome 16q12, has been identified as Nucleotide Oligomerization Domain 2 (NOD2) [2] . Three polymorphisms of this gene (R702W, G908R, and 1007fs) increase the susceptibility to IBD, especially CD.The IBD3 region on chromosome 6p was initially described in a large European cohort [3] by Hampe and coworkers, who suggested that this observation was consistent with single nucleotide polymorphism (SNPs) in either the Human Leukocyte Antigen (HLA) and/or tumor necrosis factor (TNF) genes as being risk factors for IBD. Rioux et al [4] confirmed this association in a gen...

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“…Interestingly, this variant was also associated with CD when they left out the common NOD2 allele carriers, meaning that these genes act independently to confer CD susceptibility. Pediatric onset, colonic disease and familial aggregation of CD was associated with the c.-863C>A polymorphism, which is located within a binding site for NF B in the TNF promoter [124]. Moreover, it was demonstrated that exposure of 293T cells to bacterial components stimulates TNF gene transcription as a result of NOD2-induced NF B activation [125].…”

Section: Tnf (6p)mentioning

confidence: 99%

Genetics of Spondyloarthropathies and Inflammatory Bowel Disease: Searching for Common Susceptibility Factors

Laukens¹,

Vos

2008

CRR

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Ileocolonoscopic evidence for subclinical gut inflammation is found in a subpopulation of spondyloarthropathy (SpA) patients. The prevalence of microscopic intestinal lesions is even higher and can be classified as either an acute or a chronic type of inflammation. The latter condition is associated with an increased risk of developing overt inflammatory bowel disease (IBD), especially Crohn's disease (CD), over time. Evidence for genetic predisposition in both SpA and IBD is strong, and has resulted in the identification of several linked chromosomal loci and putative candidate genes. The regular co-existence of SpA and IBD within the same family suggests a common genetic component. Interestingly, comparison of genome-wide linkage and association data reveals thirteen disease-associated chromosomal regions that are shared between SpA and IBD. This should convince geneticists to examine genes within these regions as potential susceptibility genes for the development of both SpA and IBD. Significant association of such shared genetic determinants was established for NOD2 (16q), the major histocompatibility complex I allele HLA-B27 (6p) and recently also the interleukin 23 receptor (1p). Transgenic animals in which tumor necrosis factor alpha or HLA-B27 is overexpressed suffer both joint and gut abnormalities resembling human SpA/CD pathology, providing additional evidence for a common genetic predisposition for the onset of joint and gut inflammation. In view of a hypothetical pathway leading to intestinal and articular inflammation in SpA and IBD, we review and compare genome-wide linkage and genetic association data obtained for SpA and IBD.Keywords: Spondyloarthropathy, Crohn's disease, genetic susceptibility, NOD2, HLA-B27, IL23R.Spondyloarthropathy (SpA) and inflammatory bowel disease (IBD) are chronic inflammatory conditions in which the initiating events are complex. In SpA, the axial skeleton, the sacroiliac joints and, to a lesser degree, peripheral joints become inflamed, whereas in IBD involving Crohn's disease (CD) and ulcerative colitis (UC), the intestine is the primary site of inflammation. The estimated prevalence in Western countries is 0.3-2% for SpA and 0.1-0.3% for IBD. The unity between SpA and IBD is illustrated by a strong clinical as well as molecular overlap. The first symptoms present themselves in early adulthood, usually before the age of 30, but early childhood and late onset disease occur sporadically. Medical treatment is mainly based on diminishing the inflammation and maintaining the remission states. Spondyloarthropathy is a heterogeneous group generally divided into 5 disease categories: ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA), SpA associated with IBD (SpA-IBD) and undifferentiated SpA. In the SpA-IBD group, patients suffer from clinically overt CD or UC. However, the gut is also an important site of inflammation in patients belonging to the other SpA disease categories. In ileocolonoscopic studies of SpA patients, histological ...

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A Polymorphism in the TNF-alpha Promoter Gene is Associated with Pediatric Onset and Colonic Location of Crohn's Disease

Cited by 42 publications

References 39 publications

Polymorphisms in the TNF-α Promoter and Variability in the Granulomatous Response in Patients with Crohn's Disease

Polymorphisms in the TNF-α Promoter and Variability in the Granulomatous Response in Patients with Crohn's Disease

Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

Genetics of Spondyloarthropathies and Inflammatory Bowel Disease: Searching for Common Susceptibility Factors

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