Vitamin D receptor gene polymorphism and ulcerative colitis susceptibility in Han Chinese

OBJECTIVE: Specific polymorphisms in the vitamin D receptor (VDR) gene have been associated with genetic susceptibility to inflammatory bowel disease (IBD) in different ethnic populations. METHODS: A total of 218 ulcerative colitis (UC) patients and 251 healthy controls were genotyped for VDR gene polymorphisms using PCR‐restriction fragment length polymorphism (PCR‐RFLP) assay. VDR gene polymorphisms (Apa I, Taq I, Bsm I and Fok I) were analyzed for both genotypic and phenotypic susceptibilities. RESULTS: Among the four examined VDR gene polymorphisms, the Bsm I polymorphism showed a slightly higher distribution in our study population than that in the previous studies. We also found that the increased frequency of the Bb genotype of the Bsm I VDR gene polymorphism was associated with UC in Han Chinese, as compared with healthy controls (28.4% vs. 18.7%, χ² = 6.044, P = 0.014, OR = 1.739, 95% CI = 1.122–2.697). Moreover, Bsm I polymorphic allele (B) frequency was significantly increased in the UC cases, as compared to the healthy controls (14.7% vs. 7.8% χ² = 6.222, P = 0.013; OR = 1.670, 95% CI = 1.113–2.506). In contrast, the other three VDR gene polymorphisms (Apa I, Taq I and Fok I) were not associated with UC susceptibility in the Han Chinese cohort. In addition, none of these four VDR polymorphisms had statistical association with clinicopathological parameters of these UC patients. CONCLUSION: This study demonstrated a probable association of the Bsm I polymorphism of the VDR gene with ulcerative colitis susceptibility in Han Chinese.     

Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility

BACKGROUND: The vitamin D receptor (VDR) gene represents a strong positional candidate susceptibility gene for inflammatory bowel disease (IBD). The VDR gene maps to a region on chromosome 12 that has been shown to be linked to IBD by genome screening techniques. It is the cellular receptor for 1,25(OH)(2) vitamin D(3) (calcitriol) which has a wide range of different regulatory effects on the immune system. IBD is characterised by activation of the mucosal immune system. AIM: To determine if polymorphisms in the VDR gene are associated with susceptibility to IBD SUBJECTS: European Caucasoids: 158 patients with ulcerative colitis, 245 with Crohn's disease, and 164 cadaveric renal allograft donor controls. METHOD: Single nucleotide polymorphisms (TaqI, ApaI, and FokI) in VDR were typed in patients with Crohn's disease, ulcerative colitis, and controls by polymerase chain reaction with sequence specific primers. RESULTS: There were significantly more homozygotes for the TaqI polymorphism at codon 352 of exon 8 (genotype "tt") among patients with Crohn's disease (frequency 0.22) than patients with ulcerative colitis (0.12) or controls (0.12) (odds ratio 1.99; 95% confidence interval 1.14-3.47; p=0.017). CONCLUSION: This study provides preliminary evidence for a genetic association between Crohn's disease susceptibility and a gene that lies within one of the candidate regions determined by linkage analysis.     

The frequency of C3435T MDR1 gene polymorphism in Iranian patients with ulcerative colitis

Back ground and Aims The MDR1 (multidrug resistance) gene, located on chromosome 7, is in one of the inflammatory bowel disease susceptibility loci. It produces P-glycoprotein, a transmembrane efflux pump, transferring drugs and toxins from intracellular to extracellular domains. In the human gastrointestinal (GI) tract, P-glycoprotein is found in high concentrations on the epithelial cells of the colon and small intestine. MDR1 gene polymorphisms such as C3435T are associated with lower P-glycoprotein expression, and thus it is suggested to have an association with ulcerative colitis. We tried to determine the frequency of C3435T polymorphism of the MDR1 gene in Iranian patients with ulcerative colitis and to compare it with a healthy control population. Materials and methods In this case–control-designed study, 300 unrelated ulcerative colitis patients and 300 sex-and-age-matched healthy controls were enrolled. They were visited at a tertiary center during a 2-year period (2003–2005). DNA of patients and controls was amplified by polymerase chain reaction with specific primers, and C3435T polymorphism was detected by the restriction fragment length polymorphism method. Results The frequency of the 3435T allele was significantly higher in ulcerative colitis patients compared to the controls (p < 0.001). The frequency of homozygote T/T and heterozygote C/T genotypes were also significantly higher in Iranian patients with ulcerative colitis (p = 0.044 and 0.041, respectively). Conclusion This study suggests that C3435T polymorphism of the MDR1 gene has an association with ulcerative colitis in Iranian population as previously reported in western countries.     

Association of Plasminogen Activator Inhibitor-1 Gene Polymorphism with Inflammatory Bowel Disease in Iranian Azeri Turkish Patients

Background/Aim:

Previous studies have shown the association of some genetic factors, such as Plasminogen activator inhibitor type-1 (PAI-1) 4G/5G polymorphism, with the development of inflammatory bowel disease (IBD). We aimed to study this polymorphism as a risk factor in IBD patients in this cohort.

Patients and Methods:

One hundred and fifteen IBD patients and 95 healthy controls were selected from Iranian Azeri Turks and -6754G/5G polymorphism of PAI-1 gene was tested by polymerase chain reaction using allele-specific primers confirmed by sequencing.

Results:

There was no significant difference of PAI-1 polymorphism between IBD patients and the control group (P > 0.05). Furthermore, these data showed no significant difference between Crohn''s disease and ulcerative colitis patients. However, 4G/4G homozygotes have reduced probability to progression of loss of appetite, whereas 5G/5G genotypes have increased risk for development of chronic diarrhea without blood, nausea, and loss of appetite.

Conclusions:

Although our study showed no significant association of PAI-1 polymorphism between patients and control group, the carriers of 4G/4G genotype and 4G allele had reduced risk for the progression of IBD features in this cohort.     

Bactericidal Permeability Increasing Protein Gene Polymorphism is Associated with Inflammatory Bowel Diseases in the Turkish Population

Background/Aims:

Inflammatory bowel disease, a chronic inflammatory disease with unknown etiology, affects the small and large bowel at different levels. It is increasingly considered that innate immune system may have a central position in the pathogenesis of the disease. As a part of the innate immune system, bactericidal permeability increasing protein has an important role in the recognition and neutralization of gram-negative bacteria. The aim of our study was to investigate the involvement of bactericidal permeability increasing protein gene polymorphism (bactericidal permeability increasing protein Lys216Glu) in inflammatory bowel disease in a large group of Turkish patients.

Patients and Methods:

The present study included 528 inflammatory bowel disease patients, 224 with Crohn''s disease and 304 with ulcerative colitis, and 339 healthy controls.

Results:

Bactericidal permeability increasing protein Lys216Glu polymorphism was found to be associated with both Crohn''s disease and ulcerative colitis (P = 0.0001). The frequency of the Glu/Glu genotype was significantly lower in patients using steroids and in those with steroid dependence (P = 0.012, OR, 0.80; 95% confidence interval [CI]: 0.68-0.94; P = 0.0286, OR, 0.75; 95% CI: 0.66-0.86, respectively). There was no other association between bactericidal permeability increasing protein gene polymorphism and phenotypes of inflammatory bowel disease.

Conclusions:

Bactericidal permeability increasing protein Lys216Glu polymorphism is associated with both Crohn''s disease and ulcerative colitis. This is the first study reporting the association of bactericidal permeability increasing protein gene polymorphism with steroid use and dependence in Crohn''s disease.     

Absence of association between the multidrug resistance (MDR1) gene and inflammatory bowel disease

Objective. The multidrug resistance (MDR1) gene encodes for P-glycoprotein, a drug efflux pump. Mice deficient for the MDR1a gene spontaneously develop colitis. In humans, a polymorphism in exon 26 (C3435T) is associated with reduced expression levels and function of MDR1. Currently there are controversial data on the association between MDR1 and inflammatory bowel disease (IBD). The purpose of this study was to examine the involvement of this gene in IBD in a large population of Dutch patients with IBD and family-based controls. Material and methods. A total of 781 IBD cases and 315 controls were investigated. CD phenotypes were determined according to the Vienna Classification. Individuals were genotyped for six single nucleotide polymorphisms (SNPs) close to and in the MDR1 locus. This included the C3435T variant and six microsatellite markers close to and in the MDR1 locus. Single locus association analysis, haplotype association analysis and haplotype sharing statistic (HSS) were used to search for differences between patients and controls. Results. No association was observed for any of the SNPs with IBD as a group, or for ulcerative colitis, Crohn's disease and Crohn's disease phenotypes, either by single locus or haplotype association analysis or by HSS. Conclusions. No association was observed between the MDR1 gene and IBD. This suggests that it is unlikely that MDR1 plays a role in IBD susceptibility.     

TNF-Alpha Gene Polymorphisms in Iranian Azari Turkish Patients with Inflammatory Bowel Diseases

Context:

Crohn''s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the bowel (IBD) whose causes are not fully known. Emerging data indicate that alterations in cytokine synthesis may play a role in IBD pathogenesis.

Aims:

We aimed to determine the association between tumor necrosis factor-alfa (TNFα) promoter polymorphisms (at positions − 308 and − 1031) and susceptibility to IBD among Iranian Azari Turkish patients.

Settings and Design:

One hundred and one patients with IBD and 100 healthy subjects were analyzed.

Materials and Methods:

Both polymorphisms in the promoter region of the TNFα gene at positions -1031T/C and -308G/A were detected by polymerase chain reaction-restriction fragment length polymorphism assay. All statistical analyses were calculated with SPSS for Windows 16.0. The Fisher''s exact test was used to test for departure from Hardy–Weinberg equilibrium of the genotype frequencies (P > 0.05).

Results:

The allele frequency of the TNFα-308G and -1031T were higher in IBD patients but did not reach statistical significance. However, the homozygous TT genotype for the SNP-1031 T > C was significantly higher in UC patients than in healthy controls (P = 0.01) and the heterozygous CT genotype for the SNP -1031 T > C was significantly lower in UC patients than in healthy controls (P = 0.03).

Conclusions:

The TNFα-1031 T allele confers a significant risk for developing UC in Iranian Azeri Turkish patients. Also the frequency of TNFα-1031 C allele was considerably low among patients with UC and it may have protective role among them (OR = 0.43; P = 0.01).     

No association of vitamin D receptor gene start codon fok 1 polymorphisms in Chinese patients with systemic lupus erythematosus

OBJECTIVE: To examine whether the start codon Fok I of the vitamin D receptor (VDR) gene polymorphism is a marker of susceptibility to or severity of systemic lupus erythematosus (SLE) in Chinese patients in Taiwan. METHODS: A control group of 90 healthy people and 52 patients with SLE were examined. Using polymerase chain reaction (PCR) based restriction analysis, we evaluated the relationship between Fok I polymorphisms and SLE, where an unexcisable length was determined to be 265 bp (FF), and the 2 fragments measuring 169 bp and 96 bp were determined to be excisable lengths (ff). RESULTS: For the genotype of VDR Fok I start codon polymorphism, there were no statistically significant differences between the 2 groups (chi-squared test, p = 0.07). Additionally, we did not detect any association of VDR genotype with the clinical and laboratory profiles in SLE patients. CONCLUSION: Our results suggest that the vitamin D receptor Fok I start codon polymorphism is not related to patients with SLE in Taiwan.     

Familial occurrence and inheritance studies in inflammatory bowel disease

A number of studies have demonstrated aggregation of cases of ulcerative colitis or Crohn's disease in families, and of cases of both diseases within the same families, suggesting that patients share a genetic background. Perhaps because of differences in the selection of patients, study design and diagnostic criteria, different patterns of occurrence of inflammatory bowel disease (IBD) have been found among relatives of patients with these disorders. In recent years, however, several studies have been carried out, aiming by epidemiological methods to reveal (1) the frequency of familial occurrence of IBD among patients with ulcerative colitis and Crohn's disease, and (2) the prevalence of IBD among 1⁰ relatives to patients with these diseases. Results from these studies show a relatively uniform pattern of family occurrence in about 10% of patients with ulcerative colitis and Crohn's disease, and a prevalence among 1⁰ relatives of about 10 times that of the background population. A twin study reported a significantly higher concordance rate for Crohn's disease than for ulcerative colitis in monozygotic twins. By use of complex segregation analyses in 3 different studies, a very similar model of inheritance was found to fit for ulcerative colitis, namely a major dominant or additive gene with a low penetrance. For Crohn's disease the best-fitting model was a major recessive gene, with a high penetrance. This difference strongly supports the concept of ulcerative colitis and Crohn's disease as two separate disease entities. The occurrence of both diseases within the same families in certain members of the affected families is difficult to explain. The search for distinct associations of HLA genes with inflammatory bowel disease has shown a positive correlation between DR2 and ulcerative colitis and a negative association with DR4 and DRw6, compared with ethnically matched controls. In contrast, in Crohn's disease a positive association with the combination of DR1 and DQw5 alleles was revealed, thus indicating genetically different disease susceptibility for the two disorders. In general, however, no consistent pattern has been revealed from studies of association of HLA-A or -B antigens or blood group and serum protein markers. In two French families with several members affected with Crohn's disease no evidence for an HLA haplotype association could be revealed. Possible inherited markers of ulcerative colitis or Crohn's disease have been sought but without convincing success. Increased intestinal permeability, presence of anticolon antibodies and presence of antineutrophil leukocyte antibodies have been proposed, but not proved. Thorough studies are now needed of multimember families with disease for linkage studies to identify loci which contribute to increased liability. Such studies are in progress in different centres.     

Candidate genes colocalized to linkage regions in inflammatory bowel disease

BACKGROUND/AIMS: The genes encoding for tumor necrosis factor-alpha (TNF-alpha), epidermal growth factor receptor (EGFR) and the vitamin D receptor (VDR) are colocalized to inflammatory bowel disease-associated linkage regions on chromosomes 6, 7 and 12. An association study of these gene polymorphisms with ulcerative colitis or Crohn's disease and a stratification according to disease phenotypes was performed in order to identify genetically homogenous subgroups. PATIENTS AND METHODS: 119 healthy, unrelated controls, 95 patients with Crohn's disease and 93 patients with ulcerative colitis were genotyped for the (G to A) -308 TNF-alpha promoter polymorphism on chromosome 6, the codon 497 EGFR polymorphism on chromosome 7 and the TaqI polymorphism of the VDR gene on chromosome 12. After genotyping, patients were stratified according to the respective disease phenotype. RESULTS: A disequilibrium in the distribution of the VDR genotypes was found in patients with ulcerative colitis compared to controls (p = 0.024). In fistulizing and fibrostenotic Crohn's disease the 'TT' genotype was significantly reduced compared with other phenotypes (p = 0.006), whereas the 'tt' genotype was found more frequently (p = 0.04). The frequency of the WT allele of the EGFR gene was significantly higher in ulcerative colitis (p = 0.04) than in controls. Further significant differences, concerning the associations of the different polymorphisms and disease susceptibility or clinical phenotypes, were not observed. CONCLUSIONS: Regardless of the disease phenotype, the associations between the polymorphisms and inflammatory bowel disease investigated herein are modest, even after stratification for the disease phenotypes. Hence, these polymorphisms are unlikely to confer the reported linkage between inflammatory bowel disease and chromosomes 6, 7 and 12.     

Polymorphonuclear leukocyte function in ulcerative colitis and Crohn's disease

The aim of this study was to determine whether polymorphonuclear leukocyte chemotaxis, adhesion, and electrophoretic mobility were altered in inflammatory bowel disease and whether such alterations could be related to prior ingestion of immune complexes. Polymorphonuclear leukocytes from patients with ulcerative colitis and Crohn's disease showed significantly impaired stimulated migration (P<0.05), increased adhesiveness (P<0.01 in ulcerative colitis,P<0.001 in Crohn's disease), and reduced electrophoretic mobility (P<0.02 in ulcerative colitis,P<0.001 in Crohn's disease) compared with healthy controls. The disease control of patients with rheumatoid arthritis demonstrated reduced stimulated migration (P<0.025) but normal adhesion. Preincubating normal cells in inflammatory bowel disease sera suggested that the altered migration and adhesion were due to circulating serum factors. Circulating immune complexes, detected by the C1q PEG binding assay, were present in 12.5% of patients with ulcerative colitis and 30% with Crohn's disease. Direct immunofluorescence of polymorphonuclear leukocytes suggested binding and/or ingestion of complexes in 57% of patients with ulcerative colitis, and 67% with Crohn's disease. There was a dorect correlation between positive immunofluorescence and impaired cell migration in ulcerative colitis (P<0.05), but no such relationship was found in the other parameters of polymorph function.     

Frequency of three common mutations of CARD15/NOD2 gene in Iranian IBD patients.

BACKGROUND: The CARD15/NOD2 gene, located on the pericentromeric region of chromosome 16 (IBD1) has been reported to have an association with IBD, especially Crohn's disease. Three common mutations of CARD15 are variably associated with Crohn's disease in different ethnic groups. We evaluated the frequency of these mutations (R702W, G908R and 1007fsinsC) in Iranian IBD patients and compared it with the healthy control population. METHODS: One hundred patients with ulcerative colitis, 40 patients with Crohn's disease, and 100 sex- and age-matched controls were enrolled from a tertiary center during a one-year period (2005-2006). The three mutations were assessed in DNA of leukocytes by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of R702W mutation was significantly higher in Iranian patients with Crohn's disease (p< 0.001; OR 19.21; 95% CI 4.23-87.32) compared to healthy controls. No association was observed between the other mutations and Crohn's disease and none of these mutations was associated with ulcerative colitis. CONCLUSION: The R702W mutation of CARD15 gene was associated with Crohn's disease in the Iranian population.     

A functional polymorphism in UGT1A1 related to hyperbilirubinemia is associated with a decreased risk for Crohn's disease

BackgroundAn imbalance between the production of reactive oxygen species (ROS) and their capturing by antioxidants results in oxidative stress, this may play an important role in the pathogenesis of inflammatory bowel disease (IBD). Since bilirubin is an important endogenous antioxidant, increased levels of bilirubin may protect against IBD. UDP-glucuronosyltransferase 1A1 (UGT1A1) is the only enzyme involved in the conjugation of bilirubin and the common UGT1A1*28 allele in the UGT1A1 gene, which is strongly associated with Gilbert's syndrome in Caucasians, results in elevated plasma bilirubin levels.AimsTo test the hypothesis that the UGT1A1*28 allele is associated with lower disease susceptibility to, and disease behavior within, IBD. In addition, a possible altered risk for developing IBD-drug related side-effects was explored.MethodologyGenomic DNA of 751 patients with IBD (209 patients with ulcerative colitis and 542 patients with Crohn's disease) and 930 healthy controls was genotyped for the UGT1A1*28 promoter polymorphism, and genotype distribution was compared between patients and controls. Genotype phenotype interactions were also investigated.ResultsPatients with Crohn's disease significantly less often bear the UGT1A1*28 homozygous genotype compared to the control group, with an odds ratio of 0.64, 95% CI: 0.42–0.98. The ulcerative colitis group showed no significant differences compared to controls.ConclusionThe homozygous state of the UGT1A1*28 polymorphism, associated with higher serum bilirubin levels, may be protective for the development of Crohn's disease, suggesting that the anti-oxidant capacity of bilirubin may play a part.     

−137 (G/C) IL-18 promoter polymorphism in patients with inflammatory bowel disease

Objective. There is strong evidence that genetic factors contribute to the susceptibility for inflammatory bowel diseases (IBD). Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammatory diseases such as sepsis, asthma and adult-onset Still's disease. The aim of this study was to determine whether the ?137 (G/C) IL-18 promoter polymorphism was associated with IBD susceptibility. Material and methods. For association analysis, 470 patients with Crohn's disease (CD), 235 unrelated patients with ulcerative colitis (UC) and 347 controls were enrolled. Furthermore, 233 UC and 470 CD trios were included for segregation analysis. Genotyping was performed by application of the TaqMan MGB biallelic discrimination system. Results. When comparing genotype frequencies of CD and UC patients versus controls, no significant difference was found (p=0.089 and p=0.078, respectively). However, the Cochran-Armitage trend test revealed a rising probability for CD and UC with increasing number of G alleles (p=0.030 and 0.028, respectively) for the case-control analysis. On the contrary, the family-based transmission disequilibrium test (TDT) did not show an association of the G allele with CD or UC in 470 CD and 233 UC trios (p=0.53 and p=0.79, respectively). Conclusion. The ?137 (G/C) IL-18 promoter polymorphism is not a susceptibility factor for IBD in a German cohort.     

Incidence of inflammatory bowel disease in northern France (1988-1990).

There were no data concerning the incidence of inflammatory bowel disease (IBD) in France. The aim of this study was to investigate the incidence of Crohn''s disease and ulcerative colitis in northern France. This prospective population based study was realised through the gastroenterologists of the region Nord-Pas de Calais and the Somme Department. Each gastroenterologist referred patients consulting for the first time with clinical symptoms compatible with IBD. Data were collected by an interviewer practitioner present at the gastroenterologist''s consulting room. Two independent expert gastroenterologists assessed each case in a blind manner and made a final diagnosis of Crohn''s disease, ulcerative colitis, ulcerative proctitis, or unclassifiable chronic colitis. From 1988 to 1990, 1291 cases of IBD were recorded: 674 (52%) Crohn''s disease, 466 (36%) ulcerative colitis including 162 proctitis (35%), and 151 (12%) unclassifiable chronic colitis. The mean annual incidence was 4.9 per 100,000 for Crohn''s disease and 3.2 for ulcerative colitis. The sex ratio F/M was 1.3 for Crohn''s disease and 0.8 for ulcerative colitis. The highest age specific incidence rate for Crohn''s disease was between 20 and 29 years: 13.1 for women and 9.8 for men. The highest age specific incidence rate for ulcerative colitis was between 20 and 39 years: 5.5 for women and 6.5 for men. This first French prospective study has shown an incidence rate for Crohn''s disease comparable with that seen in north European studies but lower than that seen for ulcerative colitis. These results could be related to the different environmental factors or the genetic background of the population studied, or both.     

Genetic variants of membrane metallopeptidase genes in inflammatory bowel diseases

Background

The substance P pathway modulates neuroimmune interactions during intestinal inflammation.

Aims

To analyse mucosal expression and genetic variants of the genes coding for substance P, neurokinin-1 receptor and neutral endopeptidase in patients with inflammatory bowel disease.

Methods

qRT-PCR was used to analyse mRNA levels in matched, paired samples of inflamed colonic mucosa and adjacent non-inflamed endoscopic tissue from 26 Crohn's disease and 25 ulcerative colitis patients. Allele and genotype frequencies of tag-SNPs were determined in 908 Crohn's disease, 929 ulcerative colitis, and 853 controls. Expression levels and genotype distributions were examined within patients’ clinical sub-phenotypes.

Results

All 3 evaluated genes were overexpressed in inflamed tissues from Crohn's disease (P = 0.033, P = 4 × 10⁻⁵, P = 0.001), while in ulcerative colitis only higher levels of the gene coding for neutral endopeptidase were statistically significant (P = 2.5 × 10⁻⁵). Smoking habit and perianal disease were significantly associated with substance P (P = 0.002) and neurokinin-1 receptor levels (P = 0.02) in Crohn's disease. Neutral endopeptidase rs701109 variant was associated with inflammatory bowel disease (Crohn's disease: P = 0.022; ulcerative colitis: P = 0.045), and with the need for colectomy in ulcerative colitis (P = 0.008, OR = 2.46, 95% CI = 1.27–4.76).

Conclusions

Genetic variants of the gene coding for neutral endopeptidase might affect the neuroimmune interaction during intestinal inflammation and influence clinical sub-phenotypes in patients with inflammatory bowel disease.     

Activation of REG family proteins in colitis

Abstract

Aims. To do a genome-wide gene expression study of active and inactive ulcerative colitis and Crohn's disease (inflammatory bowel disease – IBD) and examine the most differentially expressed genes. As the study showed an extreme upregulation of all regenerating islet-derived genes (REG proteins) in active IBD, we further studied the expression of REGs on protein level in active and inactive IBD, as well as in non-IBD (pseudomembranous) colitis. Methods. Microarray analysis was done on a total of 100 pinch biopsy samples from healthy controls and patients with Crohn's disease or ulcerative colitis. Tissue samples from IBD and pseudomembranous colitis were examined with routine histology and immunohistochemical analysis for REGIα, REGIV, DEFA6, and serotonin. Results. REG mRNAs were up to 83 times overexpressed in diseased mucosa compared with mucosa from healthy individuals. REGIα and REGIV were overexpressed at immunohistochemistry and located to different mucosal cell types. REGIα was expressed in basal half of crypts, REGIV in mid and outer parts of crypts and in surface epithelium and seems to be stored in, and secreted from, goblets. Pseudomembranous colitis samples showed similar staining patterns, and some IBD samples stained REG positive without inflammation on routine histology. Conclusions. All REG family mRNAs are upregulated in IBD. REGIα and REGIV have different cellular localization, possibly reflecting different biological functions. REG protein expression also in pseudomembranous colitis shows that REG family proteins are regulated in inflammatory injury and repair, not specifically for IBD as previously thought.     

Colicinogeny in Chronic Inflammatory Bowel Disease

Bure? J, Horák V, Bure?ová E, Fixa B, Komárková O, Hartmann M. Colicinogeny in chronic inflammatory bowel disease. Scand J Gastroenterol 1986, 21, 819-823

There are several indirect arguments for a possible role of colicins in chronic inflammatory bowel disease (IBD). Colicinogeny was therefore investigated in 54 patients with ulcerative colitis, 39 patients with Crohn's disease, and 160 clinically healthy controls. No significant difference was found among the examined groups. The leukocyte migration inhibition test (with colicins as antigens) was performed to estimate cellular hypersensitivity to colicins. Migration indices not exceeding the normal range in controls contrasted with abnormal values found in 36% of ulcerative colitis and 80% of Crohn's disease patients. The results are believed to be proof of cellular hypersensitivity of IBD patients to colicins of their own Escherichia coli strains. The importance of this finding must be further clarified.     

An unusual endoscopic diagnosis for acute epigastric pain

Chemotactic, phagocytic, and oxidative metabolic activity of exudative leukocytes was measured in patients with Crohn's disease (n = 20) and with ulcerative colitis (n = 20). Unstimulated and casein-stimulated migration in Boyden chambers did not differ from that of healthy controls (n = 21). Patients with Crohn's disease had reduced serum-independent phagocytosis compared with healthy controls (p < 0.01) and patients with ulcerative colitis (p < 0.01). Serum-dependent phagocytosis by leukocytes from patients with Crohn's disease did not differ from that in controls but was slightly increased in patients with ulcerative colitis (p < 0.02). Unstimulated leukocytes showed increased oxidative metabolic activity in both patient groups compared with controls (p < 0.01), which was negatively correlated with the disease activity in Crohn's disease (p < 0.02). The study shows that mobilized leukocytes from patients with Crohn's disease differ from those mobilized in ulcerative colitis and supports the concept of an abnormal inflammatory reaction in Crohn's disease.     

Screening of tumor necrosis factor receptor-associated factor 6 as a candidate gene for inflammatory bowel disease

Objective. The two forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are thought to arise because of an interplay of unfavorable genetic and exogenous factors. During a genome-wide linkage study of IBD, we observed a nominal linkage to chromosome 11p12-q13 that was further confirmed upon fine density mapping. This chromosomal region contains a functional IBD candidate gene coding for tumor necrosis factor receptor-associated factor 6 (TRAF6), a signal transducer regulating innate and adaptive immunity as well as bone homeostasis. Material and methods. Using denaturing high-performance liquid chromatography (dHPLC) and DNA sequencing, all exons and exon-intron boundaries of the TRAF6 gene in probands of 95 IBD families were initially screened; this material comprised 20 CD, 39 UC and 36 mixed families. Results. No nucleotide changes in the coding sequence of TRAF6 were detected, but a single-base insertion/deletion polymorphism in a polythymine stretch (containing 8 or 7 thymines, respectively) in intron 3 was identified. However, examination of an extended material of 290 unrelated CD patients, 416 UC patients and 320 healthy blood donors failed to show any association with this 7T/8T variation and IBD, nor was this polymorphism related to specific clinical features in IBD. Conclusions. Our study tends to exclude a good positional and functional candidate gene, TRAF6, as an IBD predisposing gene and lends support to the idea that the function of TRAF6 is important enough not to permit structural alterations of this mediator.