KCNN4 gene variant is associated with ileal Crohn's Disease in the Australian and New Zealand population.

Objectives: Crohn's disease (CD; MIM 266600) is one of the most common forms of inflammatory bowel disease (IBD), and represents a significant burden to health care in developed countries. Our aim was to determine whether a gene in the IBD linkage region on chromosome 19q13, with a role in Paneth cell secretion and T-cell activation, conferred genetic susceptibility to the development of CD.

Methods: In total, 792 CD cases and 1,244 controls of Australian origin (Caucasian) were genotyped for seven single-nucleotide polymorphisms (SNPs) in the gene encoding the intermediate conductance calcium-activated potassium channel protein (KCNN4) at 19q13.

Clinical factors predicting disease course in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease of uncertain etiology that is clinically heterogeneous and displays phenotypic change over time. With the advent of increasingly effective medical therapies, considerable research has focused on identifying patients at risk of developing a complicated course who could be targeted for early aggressive therapy. The evaluated paper identified several clinical factors associated with progression to complicated intestinal disease, including perianal disease, smoking, steroid use and early azathioprine therapy.

The Asia-Pacific consensus on ulcerative colitis.

Inflammatory bowel disease (IBD) is increasing in many parts of the Asia-Pacific region. There is a need to improve the awareness of IBD and develop diagnostic and management recommendations relevant to the region. This evidence-based consensus focuses on the definition, epidemiology and management of ulcerative colitis (UC) in Asia.

Dietary factors in chronic inflammation: food tolerances and intolerances of a New Zealand Caucasian Crohn's disease population.

Diet is known to play a major role in the symptoms of the inflammatory bowel disease, Crohn's disease (CD). Although no single diet is appropriate to all individuals, most CD patients are aware of foods that provide adverse or beneficial effects. This study seeks to categorise foods in relation to their effects on symptoms of CD, in a New Zealand Caucasian population.

Population-based cases control study of inflammatory bowel disease risk factors.

Background And Aim: The rapid increase in inflammatory bowel disease (IBD) incidence confirms the importance of environment in its etiology. We aimed to assess the role of childhood and other environmental risk factors in IBD.

Methods: A population-based case-control study was carried out in Canterbury, New Zealand.

Association of higher DEFB4 genomic copy number with Crohn's disease.

Objectives: Human beta-defensin 2 (hBD-2 or DEFB4) is a highly inducible, antimicrobial peptide, which may have an important role in the innate immune response at epithelial surfaces. Genomic copy number of DEFB4 is polymorphic, with most individuals possessing 3-5 copies. Increased DEFB4 copy number is a susceptibility factor for psoriasis, whereas a single study in a Crohn's disease (CD) cohort reported that decreased DEFB4 copy number is associated with colonic inflammation.

Genetic analysis of MDR1 and inflammatory bowel disease reveals protective effect of heterozygous variants for ulcerative colitis.

Background: Single nucleotide polymorphisms (SNPs) in the multidrug transporter MDR1 have been associated with inflammatory bowel disease (IBD) in different studies. However, the data are highly controversial. Recently, 6 haplotype tagging SNPs (tSNPs), representing the haplotype variations of the MDR1 gene, were identified.

Mushroom intolerance: a novel diet-gene interaction in Crohn's disease.

Carrying a functional single nucleotide polymorphism (L503F, c. 1672 C>T) in the gene for the Na-dependent organic cation transporter (OCTN1), increases the risk of Crohn's disease (CD) in some, but not all, populations. Case-control data on New Zealand Caucasians show no differences for CD risk between individuals carrying the L503F OCTN1 C-allele when compared with those carrying the variant T-allele.

World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD in 2010.

Inflammatory bowel disease (IBD) represents a group of idiopathic, chronic, inflammatory intestinal conditions. Its two main disease categories are: Crohn's disease (CD) and ulcerative colitis (UC), which feature both overlapping and distinct clinical and pathological features. While these diseases have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades.

Tumor necrosis factor receptor superfamily, member 1B haplotypes increase or decrease the risk of inflammatory bowel diseases in a New Zealand caucasian population.

Inflammatory bowel diseases (IBDs) comprising Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions with polygenic susceptibility. Interactions between TNF-alpha and TNF-alpha receptor play a fundamental role in inflammatory response. This study investigates the role that selected single nucleotide polymorphisms (SNPs) and haplotypes in the TNF-alpha receptor (TNSFRSF1B) gene play in the risk of IBD in a New Zealand Caucasian population.

Nucleotide-binding oligomerization domain containing 1 (NOD1) haplotypes and single nucleotide polymorphisms modify susceptibility to inflammatory bowel diseases in a New Zealand caucasian population: a case-control study.

Background: The nucleotide-binding oligomerization domain containing 1 (NOD1) gene encodes a pattern recognition receptor that senses pathogens, leading to downstream responses characteristic of innate immunity. We investigated the role of NOD1 single nucleotide polymorphisms (SNPs) on IBD risk in a New Zealand Caucasian population, and studied Nod1 expression in response to bacterial invasion in the Caco2 cell line.

Findings: DNA samples from 388 Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis patients and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common SNPs in NOD1, using the MassARRAY iPLEX Gold assay.

Interactions among genes influencing bacterial recognition increase IBD risk in a population-based New Zealand cohort.

Bacterial sensing is crucial for appropriate response by the innate and adaptive immune system against invading microorganisms. Single nucleotide polymorphisms (SNPs) in genes involved in bacterial recognition, CARD15 and TLR4, increased the risk of inflammatory bowel disease (IBD) in a New Zealand Caucasian case-control cohort. We now consider the effects of SNPs in CD14, TLR9, and BPI, analyzed individually, in association with one another, and with SNPs in CARD15 or TLR4 in this same population group.

Reduction of dietary poorly absorbed short-chain carbohydrates (FODMAPs) improves abdominal symptoms in patients with inflammatory bowel disease-a pilot study.

Objective: Functional gut symptoms are common in patients with inflammatory bowel disease (IBD). Since poorly absorbed, short-chain carbohydrates (FODMAPs) appear to play an important role in the induction of functional gut symptoms, we aimed to determine the effect of their dietary restriction on abdominal symptoms in patients with stable IBD and to examine factors associated with success of and adherence to the diet.

Material And Method: 52 consecutive patients with Crohn's disease and 20 with ulcerative colitis who received dietary advice at least 3 months prior at a gastrointestinal dietetic service in Victoria, Australia, underwent a retrospective telephone questionnaire.

Perianal disease predicts changes in Crohn's disease phenotype-results of a population-based study of inflammatory bowel disease phenotype.

Background: The Montreal classification system of inflammatory bowel disease (IBD) provides a framework for describing disease phenotype.

Objective: We aimed to describe changes in IBD phenotype using the Montreal system and determine predictors of phenotype change in a Caucasian population-based cohort.

Methods: Ninety-two percent of people with IBD in Canterbury, New Zealand were recruited.

Severe hepatotoxicity with high 6-methylmercaptopurine nucleotide concentrations after thiopurine dose escalation due to low 6-thioguanine nucleotides.

Azathioprine and its initial metabolite, 6-mercaptopurine (6-MP), are associated with high rates of treatment cessation due to toxicity or inadequate response. Individualization of thiopurine dose based on concentrations of the active 6-thioguanine nucleotide (6-TGN) metabolites can help improve outcomes with this class. Some individuals, however, preferentially metabolize thiopurine drugs to the potentially hepatotoxic 6-methylmercaptopurine nucleotide (6-MMPN) metabolites rather than the 6-TGNs.

Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome.

Aim: To determine whether Lactobacillus casei strain Shirota (Yakult) can alter small intestinal bacterial overgrowth (SIBO), as tested by the lactulose breath test, and whether this is associated with changes in symptoms in irritable bowel syndrome (IBS).

Methods: 18 patients with IBS (Rome II criteria), who showed an early rise in breath hydrogen with lactulose (ERBHAL), consumed 65 mL of Yakult daily for 6 wk. Lactulose breath test was repeated at the end of the treatment period.

Thiopurine hepatotoxicity in inflammatory bowel disease: the role for adding allopurinol.

Background: Immunomodulator therapy with the thiopurine analogues azathioprine or 6-mercaptopurine is commonly prescribed for the treatment of inflammatory bowel disease (IBD). Drug adverse effects and the lack of efficacy, however, commonly require withdrawal of therapy. Allopurinol, a xanthine oxidase inhibitor, was recently evaluated in its role in modifying thiopurine metabolism and improving drug efficacy in IBD.

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

Aim: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-alpha) 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-alpha receptor: -238 G-->A, -308 G-->A and -857C-->T, using a Taqman assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies.

Review of fecal biomarkers in inflammatory bowel disease.

Purpose: We reviewed potential fecal biomarkers of inflammatory bowel disease and assessed their utility in a range of clinical applications.

Methods: A literature search using PubMed, MEDLINE, and Embase database was performed, locating all language articles on fecal biomarkers, including calprotectin and lactoferrin. The references of these papers were searched manually for further references.

Thiopurine dose in intermediate and normal metabolizers of thiopurine methyltransferase may differ three-fold.

Background & Aims: Patients with inflammatory bowel disease (IBD) may have different thiopurine dose requirements in relation to thiopurine methyltransferase (TPMT) genotype and/or phenotype. The purpose of this study was to determine thiopurine dose requirements in intermediate versus normal TPMT metabolism status.

Methods: Consecutive patients starting azathioprine or 6-mercaptopurine for IBD were followed up for 9 months.

Beyond TPMT: genetic influences on thiopurine drug responses in inflammatory bowel disease.

Azathioprine and 6-mercaptopurine are widely used in the management of inflammatory bowel disease (IBD). However, approximately 25% of IBD patients experience toxicity, and up to 10% show resistance to these thiopurine drugs. The importance of genetic variability in determining thiopurine toxicity was first recognized over 25 years ago with the discovery of the thiopurine S-methyltransferase (TPMT) polymorphism and the occurrence of azathioprine-induced myelosuppression in TPMT-deficient patients.

Trinucleotide repeat variants in the promoter of the thiopurine S-methyltransferase gene of patients exhibiting ultra-high enzyme activity.

Thiopurine S-methyl transferase (TPMT) is a cytosolic enzyme that catalyses the S-methylation of the thiopurine immunosuppressants. To date, 22 variants have been identified that are predictive of decreased TPMT activity. In contrast, no molecular explanation has been found for the 1-2% of Caucasians who exhibit ultra-high TPMT activity.