Epistasis between Toll-like receptor-9 polymorphisms and variants in NOD2 and IL23R modulates susceptibility to Crohn's disease.

Objectives: Recent data suggest functional interactions between NOD2 and other receptors of the innate immune system modulating inflammatory responses. Here we analyzed the role of Toll-like receptor 9 (TLR-9) gene variants with respect to susceptibility to inflammatory bowel disease (IBD) and tested for genetic interactions with NOD2 and other susceptibility genes for Crohn's disease (CD).

Methods: The single-nucleotide polymorphisms (SNPs) -1237T/C (rs5743836) and 2848A/G (rs352140=p.

NOD2/CARD15 genotype influences MDP-induced cytokine release and basal IL-12p40 levels in primary isolated peripheral blood monocytes.

Background: The functional link between mutations in NOD2 and Crohn's disease (CD) has not been entirely elucidated. The 1007fs mutation results in loss of NF-kappaB activation in response to muramyl dipeptide (MDP) but has also been linked to an increased IL-1beta processing and IL-12 release.

Methods: We investigated the basal and MDP-triggered mRNA expression and protein release for TNF-alpha, IL-10, IL-1beta, and IL-12p40 in peripheral blood monocytes from 40 CD patients and 15 healthy individuals with different NOD2 genotypes.

The ATG16L1 gene variants rs2241879 and rs2241880 (T300A) are strongly associated with susceptibility to Crohn's disease in the German population.

Objectives: We analyzed ATG16L1, a recently identified Crohn's disease (CD) susceptibility gene, in a large cohort with inflammatory bowel disease (IBD) including potential interactions with other IBD genes as well as factors regulating its gene expression.

Methods: Genomic DNA from 2,890 Caucasians including 768 patients with CD, 507 patients with ulcerative colitis (UC), and 1,615 healthy controls was analyzed for 9 different ATG16L1 single nucleotide polymorphisms (SNPs). Genotyping included CARD15/NOD2 variants p.

rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants.

Background: The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants.

Methods: Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs.

The 14-bp deletion polymorphism in the HLA-G gene displays significant differences between ulcerative colitis and Crohn's disease and is associated with ileocecal resection in Crohn's disease.

HLA-G is a non-classical MHC class Ib molecule predominantly expressed in cytotrophoblasts and under pathological conditions also in chronically inflamed and in malignant tissues. Recently an increased expression of HLA-G was found in ulcerative colitis (UC), but not in Crohn's disease (CD). The HLA-G gene is located in IBD3, a linkage region for inflammatory bowel disease (IBD).

Genetic variants and the risk of Crohn's disease: what does it mean for future disease management?

Genetic research in inflammatory bowel disease, especially in Crohn's disease, has made significant progress during recent years. There have been > 10 total genome scans that have been performed, and susceptibility loci on several chromosomes have been identified. Together with candidate gene studies, these scans have led to the identification of several susceptibility genes, with CARD15 being the most important.

Role of the NFKB1 -94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genes.

Background: Recently, an association of the NFKB1 polymorphism -94ins/delATTG with ulcerative colitis (UC) has been reported. This 4-bp insertion/deletion polymorphism is localized in the promoter region of the NFKB1 gene and appears to be functionally relevant. The aim of the present study was to confirm the association of the -94ins/delATTG (W/D) NFKB1 promoter polymorphism with UC in a population of German origin and to test for a potential association with Crohn's disease (CD).

Recurrent severe gastrointestinal bleeding and malabsorption due to extensive habitual megacolon.

Dilatation of the colon and the rectum, which is not attributable to aganglionosis, is a rare finding and can be the result of intractable chronic constipation. We report a rare case of a 29-year-old male patient with impressive megacolon, in whom Hirschsprung's or Chagas disease was ruled out. In the present case, dilatation of the colon was most likely due to a behavioral disorder with habitual failure of defecation.

The angiotensin I-converting enzyme gene insertion/deletion polymorphism is linked to early gastric cancer.

The insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene has recently been linked to the pathogenesis and progression of human cancers. Using genomic DNA from 88 patients with early gastric cancer confined either to mucosa (pT(1a)) or submucosa (pT(1b)), we assessed the insertion (I) and deletion (D) polymorphism by PCR analysis and compared it with a large noncancer control population (n = 145). In the noncancer control group, the II genotype was observed in 33 (23%) individuals, whereas the ID and DD genotypes were found in 72 (50%) and 40 (27%) individuals, respectively.

The leukocyte count predicts the efficacy of treatment with azathioprine in inflammatory bowel disease.

Introduction: Azathioprine has variable efficacy in inflammatory bowel disease. Previous studies suggested that either neutropenia, an increase in the mean corpuscular volume, the assessment of thiopurine methyl-transferase activity or erythrocyte 6-thioguanine values might predict the treatment response. However, due to the conflicting results of the preceding studies there are yet no established laboratory values which allow an estimation of the clinical response.

Association of polymorphisms in the interleukin-18 gene in patients with Crohn's disease depending on the CARD15/NOD2 genotype.

Unlabelled: An increased expression of interleukin-18 (IL-18), a proinflammatory cytokine inducing interferon-gamma, has been found in Crohn's disease (CD). In the IL-18 gene, several partly functional relevant polymorphisms are known. This study sought to investigate associations of IL-18 polymorphisms in inflammatory bowel disease and CD according to CARD15/NOD2 mutation status and clinical phenotypes.

Preoperative serum levels of the carcinoembryonic antigen in hereditary non-polyposis colorectal cancer compared to levels in sporadic colorectal cancer.

Background: Carcinoembryonic antigen (CEA) serves as the most widely used and most cost-effective tumor marker in colorectal cancer for almost 30 years. Recent publications about serum CEA levels are based on patient groups without definite differentiation between hereditary and non-hereditary forms of colorectal cancer.

Patients And Methods: We compared preoperative CEA serum levels from 105 patients with hereditary non-polyposis colorectal cancer (HNPCC) and 107 patients with sporadic colorectal cancer including influences of age and Dukes stage.

Prokinetic therapy: what can be measured by gastric scintigraphy?

Objective: To evaluate whether gastric scintigraphy with quantitative analysis of gastric peristalsis may be a useful tool for documenting the effects of prokinetic therapy.

Methods: Gastric emptying was determined in eight patients with insulin dependent diabetes mellitus (IDDM) and nine patients with progressive systemic sclerosis (PSS) after ingestion of a semi-solid test meal. Fourier analysis of condensed images was used to evaluate contraction amplitudes of the entire stomach, as well as frequency and velocity of gastric contractions.

Polymorphisms of the interleukin-18 gene in periodontitis patients.

Background: Interleukin (IL)-18 regulates the expression of the proinflammatory cytokine interferon (IFN)-gamma. The present study sought to test the putative involvement of six different IL-18 gene polymorphisms in pre-disposition to destructive periodontal disease.

Methods: A total of 123 patients with periodontitis and 121 healthy controls were genotyped for six IL-18 polymorphisms at position -656, -607, -137, +113, +127 and codon 35/3.

A polymorphism of the bactericidal/permeability increasing protein (BPI) gene is associated with Crohn's disease.

Background: The bactericidal/permeability increasing protein (BPI) is involved in the elimination of gram-negative bacteria. A functionally relevant single nucleotide polymorphism of the BPI gene causes an amino acid exchange (Glu216Lys).

Study: To evaluate whether this single nucleotide polymorphism contributes to the predisposition to inflammatory bowel disease, we compared the allele frequencies of 265 patients with Crohn's disease, 207 patients with ulcerative colitis, and 608 healthy controls.

Allele 2 of the interleukin-1 receptor antagonist gene is associated with early gastric cancer.

Purpose: In advanced gastric cancer (tumor stages T2-T4), associations with polymorphisms of the interleukin-1 (IL-1) gene cluster have been made. In early-stage gastric cancer, which we defined as adenocarcinoma confined to the mucosa or submucosa (stage T1), the role of host genetic susceptibility remains to be determined.

Patients And Methods: Eighty-eight patients with early-stage gastric cancer (stage T1, 77 positive for Helicobacter pylori) and 145 controls were genotyped for polymorphisms in the IL-1 gene cluster and the tumor necrosis factor alpha (TNF-A) gene.

The CD14 -159C-to-T promoter polymorphism in periodontal disease.

Background: A single-nucleotide promoter polymorphism in the CD14 gene was associated with various inflammatory conditions. The present study sought to determine the frequency of the CD14 -159C-to-T polymorphism among subjects with periodontitis and healthy control individuals.

Methods: A total of 70 patients with periodontal disease and 75 healthy controls were genotyped for the CD14 -159C-to-T polymorphism.