Association of Susceptibility Locus for Inflammatory Bowel Disease on Chromosome 16 with Both Ulcerative Colitis and Crohn's Disease

A susceptibility locus for inflammatory bowel disease (IBD) on chromosome 16 (IBD1) has been linked to Crohn's disease in genome-wide linkage studies. We performed a case–control study with two markers for this locus using leukocyte DNA from 127 Crohn's patients, 83 ulcerative colitis patients, and 74 control patients. Allele, genotype, and haplotype frequencies of the polymerase chain reaction products were determined using autoradiography. Haplotype frequencies differed for ulcerative colitis and Crohn's disease, particularly for haplotype CC (22% ulcerative colitis vs 10% Crohn's disease, P = 0.002 ² = 10.0) and haplotype CD (18% Crohn's disease vs 9% ulcerative colitis, P = 0.025 ² = 5.02). These data demonstrate the association of the IBD1 locus with both ulcerative colitis and Crohn's disease in a group of unrelated IBD patients. The use of such microsatellite markers when combined with others, might help distinguish ulcerative colitis from Crohn's disease in patients with ambiguous clinical and histological features.     

Circulating soluble vascular adhesion protein 1 in patients with inflammatory bowel disease

OBJECTIVE: A dysregulated local immune defence with a constant influx of leucocytes provides a basis for continuous intestinal inflammation in ulcerative colitis and Crohn's disease. Since vascular adhesion protein 1 (VAP-1) is one of the adhesion molecules that mediates lymphocyte binding to endothelium, we investigated the levels of soluble VAP-1 (sVAP-1) in the sera of inflammatory bowel disease (IBD) patients compared with healthy controls. METHODS: sVAP-1 serum levels were measured in 161 IBD patients (90 ulcerative colitis, 71 Crohn's disease) and 93 controls using a commercially available enzyme-linked immunosorbent assay (ELISA). sVAP-1 levels were correlated with disease activity and localization. In 42 patients, sVAP-1 levels were measured in both the active and inactive phases of the disease. RESULTS: sVAP-1 serum levels were detected in all control and IBD subjects. Mean sVAP-1 levels were 365.5 +/- 153.5 ng/ml in ulcerative colitis patients, 336.4 +/- 172.8 ng/ml in Crohn's disease patients, and 344.7 +/- 150.4 ng/ml in healthy controls. The differences between the groups were not significant. No association between disease activity or disease localization and sVAP-1 was found. CONCLUSIONS: sVAP-1 serum concentrations are not significantly different in IBD and healthy control subjects. sVAP-1 serum levels are of no value in the assessment of disease activity or severity of inflammation in patients with IBD.     

白细胞介素-23受体基因多态性与炎症性肠病关系的初步研究

目的 初步探讨白细胞介素-23受体(IL23R)基因中两个单链核苷酸多态性(SNP)位点(rs11209026和rs11805303)的遗传多态性和炎症性肠病(IBD)的发病易感性之间的关系.方法 采用聚合酶链反应(PCR)直接测序法检测50名健康人和81例IBD患者(其中克罗恩病41例,溃疡性结肠炎40例)的两个SNP位点基因多态性.结果 rs11209026位点基因型频率和等位基因频率在克罗恩病患者分别为7.3%和3.7%,在溃疡性结肠炎患者分别为15.0%和7.5%,在对照组分别为14.0%和7.0%,三组间差异均无统计学意义(P值均＞0.05).rs11805303位点的基因型频率和等位基因频率在克罗恩病患者分别为22.0%和52.4%,在溃疡性结肠炎患者分别为15.0%和41.2%,在对照组分别为34.0%和59.0%,三组间基因型频率比较差异均无统计学意义(P值均＞0.05),而等位基因频率在溃疡性结肠炎患者和对照组间差异有统计学意义(P=0.018).rs11805303位点基因多态性与溃疡性结肠炎患者的发病年龄、性别、疾病的活动性及发病部位均无关(P值均＞0.05).结论 IL23R两个SNP位点基因多态性与克罗恩病无相关性.rs11805303位点的多态性可能为溃疡性结肠炎患者的一个遗传标志,但与该病病变特点无显著相关.     

A population- and family-based study of Canadian families reveals association of HLA DRB1*0103 with colonic involvement in inflammatory bowel disease

The aim of this study was to identify major histocompatibility complex alleles associated with the development and clinical features of inflammatory bowel disease (IBD). Genotyping at the human leukocyte antigen (HLA) DRB1 and DQB1 loci was performed on individuals from 118 Caucasian IBD sibling pair families and on 216 healthy controls. Both population- and family-based association tests were used to analyze data obtained on the entire study population and on clinical subgroups stratified by diagnosis, ethnicity, and disease distribution. HLA DRB1*0103 was significantly associated with IBD (OR = 6.0, p = 0.0001) in a case-control analysis of non-Jewish IBD-affected individuals. This association was apparent among both Crohn's disease (OR = 5.23, p = 0.0007) and ulcerative colitis (OR = 7.9, p = 0.0001) patients and was confirmed in the non-Jewish IBD population by results of family-based association analysis using the transmission disequilibrium test. HLA DQB1*0501 was also associated with IBD (OR = 1.64, p = 0.02) in the non-Jewish population. but statistically significant association of this allele with disease was not detected for Crohn's disease and ulcerative colitis separately. No significant associations were identified among the Jewish patients. In the non-Jewish IBD families, IBD was as strongly associated with the DRB1*0103 DQB1*0501 haplotype as with the DRB1*0103 allele alone. The carrier frequency of the DRB1*0103 allele was found to be 10-fold higher in Crohn's disease patients with pure colonic involvement than in healthy controls (38.5% vs. 3.2%; p = 0.0002). These data demonstrate the association of the HLA DRB1*0103 allele with both Crohn's disease and ulcerative colitis and with large intestine-restricted disease in non-Jewish IBD patients and therefore identify HLA DRB1*0103 as a potentially important contributor to disease susceptibility and to expression of colonic involvement in IBD.     

Increased risk for demyelinating diseases in patients with inflammatory bowel disease

BACKGROUND & AIMS: Reports of multiple sclerosis (MS), demyelination, and optic neuritis (ON) associated with anti-tumor necrosis factor alpha therapy resulted in warnings on prescribing instructions for infliximab, etanercept, and adalimumab. However, the underlying relationship between IBD and these neurologic conditions has not been established. METHODS: We performed a retrospective cohort study and a retrospective cross-sectional study using 1988 to 1997 data from the General Practice Research Database. A total of 7988 Crohn's disease and 12,185 ulcerative colitis patients were matched for age, sex, and primary care practice to 80,666 randomly selected controls. In the cohort study, incident cases of MS, demyelination, and/or ON (MS/D/ON) had to occur at least 1 year after registration with the physician and after the diagnosis of IBD. In the cross-sectional study, the diagnosis of MS/D/ON could either precede or follow the IBD diagnosis. RESULTS: In the cohort study, the incidence of MS/D/ON was higher in patients with Crohn's disease and ulcerative colitis compared with their matched controls, reaching statistical significance for ulcerative colitis (ulcerative colitis incidence rate ratio [IRR], 2.63; 95% confidence interval, 1.29-5.15; Crohn's disease IRR, 2.12; 95% confidence interval, .94-4.50). In the cross-sectional study, MS/D/ON was more prevalent in patients with Crohn's disease and ulcerative colitis compared with their matched controls (Crohn's disease odds ratio, 1.54; 95% confidence interval, 1.03-2.32; ulcerative colitis odds ratio, 1.75; 95% confidence interval, 1.28-2.39). CONCLUSIONS: Demyelinating diseases occur more commonly among patients with IBD than among non-IBD patients. Future studies should clarify whether treatment with tumor necrosis factor alpha blockers results in further increased incidence of MS/D/ON among IBD patients.     

Elevated serum eotaxin levels in patients with inflammatory bowel disease

OBJECTIVE: Eotaxin is a recently characterized chemokine with potent and selective chemotactic activity for eosinophils. Previous studies indicating that eosinophils accumulate and become activated in inflammatory bowel disease (IBD) led us to hypothesize that eotaxin is potentially involved in the pathophysiology of IBD and, therefore, that eotaxin would be increased in the serum of patients with IBD. The objective of this study was to test those assumptions. METHODS: We investigated 72 patients with IBD, 35 with ulcerative colitis, and 37 with Crohn's disease. A total of 27 patients had active and 45 inactive disease; 26 were receiving corticosteroids. Eotaxin serum levels were determined by solid phase sandwich ELISA. Lymphocytes, monocytes, and granulocyte subpopulations were determined in fresh blood samples with an automated autoanalyzer. RESULTS: Serum eotaxin levels were significantly higher in patients with Crohn's disease and in those with ulcerative colitis than in the control subjects (p < 0.0001). Patients with inactive Crohn's disease had significantly higher levels of eotaxin than patients with inactive ulcerative colitis (p < 0.05). We did not find significant differences for activity or inactivity of disease, nor for treatment with prednisone. A negative correlation (p < 0.05) was found between eotaxin serum level and eosinophil counts in peripheral blood in patients with Crohn's disease. CONCLUSIONS: There is an increased expression of eotaxin in IBD patients, suggesting that eotaxin may be involved in the pathogenesis of IBD. This increase is more accentuated in Crohn's disease and negatively correlates with the eosinophil number in peripheral blood. Our data support the increasing evidence that eosinophil are functionally involved in the pathophysiology of IBD.     

Prevalence of inflammatory bowel disease in patients with airways disease

BACKGROUND: Case reports and case series have suggested an association between inflammatory bowel disease (IBD) and airways disease, but there are no data demonstrating a higher prevalence of IBD among patients with airways disease. Furthermore, no consistent radiological, pulmonary or pathological abnormalities have been demonstrated in patients with both conditions. AIMS: To determine the prevalence of IBD among patients with airways disease and to evaluate clinical and pathophysiological features. METHODS: A retrospective analysis of outpatients with airways disease over a 10-year period. RESULTS: IBD was four times more prevalent among patients with airways disease compared with published local IBD prevalence [Odds Ratio 4.26, 95% CI 1.48, 11.71, p=0.006; Crohn's disease OR 5.96, 95% CI 1.94, 18.31, p=0.002 and ulcerative colitis OR 4.21, 95% CI 1.71, 10.41, p=0.001]. IBD was more frequent in all types of airways disease except asthma; the association was particularly strong for conditions associated with productive cough. All except 1 patient had established IBD before the onset of respiratory symptoms. There were no obvious radiological differences between ulcerative colitis and Crohn's disease cases. There was a trend for a higher lymphocyte count (despite a tendency to lower blood lymphocyte count) but lower sputum neutrophil count in patients with Crohn's disease compared with ulcerative colitis. There were no significant differences in physiological measurements of pulmonary function between the two types of IBD. CONCLUSION: Our findings support an association between airways disease and inflammatory bowel disease, particularly non-asthmatic airways disease with productive cough.     

Passive Smoking is Associated with an Increased Risk of Developing Inflammatory Bowel Disease in Children

Adult cigarette smoking is associated with the development of Crohn's disease and protection from the development of ulcerative colitis. Children usually are nonsmokers whose risk of developing inflammatory bowel disease (IBD) may he related to passive smoking. The purpose of this matched case-control study was to evaluate passive smoking exposure in 72 nonsmoking children with recently diagnosed IBD (39 with ulcerative colitis and 33 with Crohn's disease), and in an equal number of peer-nominated controls. Passive smoking exposure at birth was significantly associated with the development of IBD (odds ratio 3.02, 95% confidence interval 1.28-7.06). The effect was greater in Crohn's disease (odds ratio 5.32) than in ulcerative colitis (odds ratio 2.19). Maternal smoking at birth also was significantly associated with the development of IBD (odds ratio 2.09,95% confidence interval 1.02–4.29), an effect that also was greater in Crohn's disease than in ulcerative colitis. There was a dose-response relationship between packs smoked per day and IBD, and packs smoked at home per day and IBD. At symptom onset, the risk of developing IBD from passive smoking exposure was increased hut was not significant (odds ratio 1.88, 95% confidence interval 0.84–4.18). The magnitude of the effect was greater in Crohn's disease than in ulcerative colitis, and the association demonstrated dose-response. In conclusion, passive smoking exposure and maternal smoking at birth and, to a lesser extent, passive smoking exposure at symptom onset are associated with an increased risk of developing IBD in children. The association is stronger in Crohn's disease than in ulcerative colitis, and there is a dose-response effect. The specific toxic exposure is more likely to he inhaled rather than passed through the placenta or in breast milk.     

Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27).

Histocompatibility (HLA) antigen phenotypes have been studied in 100 patients with ulcerative colitis, 100 with Crohn's disease, and 283 normal controls. In addition the incidence of ankylosing spondylitis, sacroiliitis, and "enteropathic" peripheral arthropathy was determined in the patients with inflammatory bowel disease (IBD). There was no significant difference in antigen frequency between patients and controls. However, the incidence of HLA-B27 was increased in the patients complicated by ankylosing spondylitis and/or sacroiliitis in both ulcerative colitis and Crohn's disease. In contrast, none of the 29 IBD patients with "enteropathic" peripheral arthropathy had B27 antigen. Furthermore, ankylosing spondylitis was found more frequently in ulcerative colitis bearing HLA-B27 compared with non-B27 patients (P less than 0-01). The same was found in Crohn's disease, although this difference was not statistically significant. In addition, 12 of 14 ulcerative colitis patients and five out of six Crohn's patients with HLA-B27 had total colitis, compared with the frequency of total colitis in non-B27 patients (P less than 0-024 and less than 0-03 respectively). The data suggest that B27 histocompatibility antigen could be a pathogenetic discriminator between the arthropathies in IBD and may be of prognostic significance with respect to extension and severity of the disease.     

Frequent detection of cytomegalovirus in the intestine of patients with inflammatory bowel disease

BACKGROUND: Although a growing number of reports have described inflammatory bowel disease (IBD) complicated with cytomegalovirus (CMV) infection, there are limited molecular studies that investigate CMV genome in intestinal sections of patients with IBD. METHODS: A cross-sectional prospective study was conducted between September 2000 and June 2003 in a cohort of 85 patients diagnosed with IBD (58 with ulcerative colitis and 27 with Crohn's disease) in two adult gastrointestinal referral centers in Athens, Greece. Prevalence of CMV infection was estimated by pathologic studies in intestinal sections and by molecular assays in blood and intestinal tissue samples and compared with a control group of 42 individuals with noninflammatory disease. RESULTS: Immunohistochemical staining showed CMV antigen in 10 IBD patients (7 with ulcerative colitis; 9 with severe disease), whereas CMV antigen was not detected in any of the controls. CMV genome in both the intestinal tissue and blood was found by polymerase chain reaction in 23 (27.1%) of the total IBD patients, in 18 (31.0%) of those with ulcerative colitis, and in 5 (18.5%) of those with Crohn's disease. In addition, five (5.9%) IBD patients (2 with ulcerative colitis and 3 with Crohn's disease) had detectable CMV genome in their intestinal samples but not in their blood. In the control group, five (11.9%) individuals had detectable CMV genome in their blood, but only one (2.2%) in his intestine. CONCLUSION: Patients with ulcerative colitis had more often detectable CMV genome in their blood as well as in their intestinal tissue samples as compared with controls (P = 0.022 and P < 0.0001, respectively). However, patients with Crohn's disease had more often detectable CMV genome only in their intestinal tissue samples as compared with controls (P = 0.001). Detection of CMV genome in blood or intestinal tissue was significantly associated with short duration of IBD (P = 0.0088 and 0.04, respectively) but not with age, sex, severity of the disease, activity at colonoscopy, pancolitis, administration of a specific treatment, and surgery. In this cross-sectional prospective study, detection of CMV genome or antigen in the intestine was commonly associated with IBD.     

细胞毒性T淋巴细胞相关抗原4基因多态性与炎症性肠病的相关性

目的 炎症性肠病(IBD)的发病机制与T细胞免疫应答过度有关。细胞毒T淋巴细胞相关抗原4(CTLA-4)主要在已激活的T细胞上表达,通过与CD28竞争与B7结合,抑制T细胞激活,维持免疫系统内环境稳定。CTLA-4基因多态性与一些自身免疫性疾病相关,但未见其与IBD的研究。本研究旨在了解IBD的遗传易感性。方法 对68例无血缘关系的湖北汉族IBD患者(54例溃疡性结肠炎,14例克罗恩病)以及140例正常对照者,采用序列特异性引物PCR方法检测CTLA-4外显子4的3’非转录区包含AT重复序列的特异性等位基因。扩增产物用12％非变性聚丙烯酰胺凝胶电泳,硝酸银染色,部分样品经测序以确定片段长度。结果 共发现CTLA4基因有18种等位基因,与正常对照组比较,122bp等位基因在溃疡性结肠炎患者中显著增高(7．4％vs0．3％,P=0．0002／Pc=Sig,OR=22．32．95％CI：2．76～180．80)。结论 CTLA-4基因微卫星多态性与溃疡性结肠炎显著相关。     

Urinary excretion of N-methylhistamine as a marker of disease activity in inflammatory bowel disease

OBJECTIVE: Mast cells are thought to participate in the pathogenesis of inflammatory bowel disease (IBD). In this study, urinary excretion of N-methylhistamine (UMH), a stable metabolite of the mast cell mediator histamine, was evaluated as an indicator of disease activity in patients with IBD. METHODS: Urinary excretion of UMH (microg/mmol creatinine x m2 body surface area) was measured by radioimmunoassay in 55 controls, 56 patients with Crohn's disease, and in 36 patients with ulcerative colitis. Excretion rates were correlated with clinical, serological, and endoscopic disease activity, disease extent, and location. RESULTS: Urinary excretion of UMH was found to be significantly elevated in IBD. Patients with active Crohn's disease (7.1 +/- 4.2, p = 0.002 vs controls) and active ulcerative colitis (8.1 +/- 4.8, p = 0.02 vs controls) had higher rates of UMH excretion than patients in remission (6.3 +/- 3.8 and 5.2 +/- 2.3, respectively) or controls (4.6 +/- 1.9). In Crohn's disease and ulcerative colitis, a significant correlation of UMH excretion with clinical disease activity was obtained (Crohn's Disease Activity Index r2 = 0.58, Clinical Activity Index r2 = 0.57, p < 0.0001). Serologically, orosomucoid showed the best positive correlation with disease activity (Crohn's Disease Activity Index r2 0.80, Clinical Activity Index r2 = 0.86, p < 0.0001), but UMH excretion was found to reflect disease activity more accurately than C-reactive protein (Crohn's Disease Activity Index r2 = 0.46, Clinical Activity Index r2 = 0.42, p < 0.0001). No association between UMH excretion and disease type or localization could be found in Crohn's disease. However, UMH excretion correlated strongly with endoscopic severity of inflammation in Crohn's disease (Crohn's Disease Endoscopic Index of Severity r2 = 0.70, p < 0.0001) or disease extent in ulcerative colitis. CONCLUSIONS: Urinary excretion of the histamine metabolite UMH is enhanced in IBD. It appears to represent an integrative parameter to monitor clinical and endoscopic disease activity in IBD, which appears to be influenced most likely by mediators released from histamine-containing cells, such as intestinal mast cell subtypes.     

Family history as a risk factor for colorectal cancer in inflammatory bowel disease

BACKGROUND & AIMS: Familial colorectal cancer (CRC) is a risk factor for CRC in healthy individuals and, as indicated by case-control studies, possibly in ulcerative colitis. Little is known about the cancer risk in familial inflammatory bowel disease (IBD). We assessed the significance of familial CRC, or IBD, on the risk for CRC in patients with IBD. METHODS: Population-based cohort study of 19,876 individuals with ulcerative colitis or Crohn's disease born between 1941 and 1995. Registry-based follow-up and assessment of familial CRC, and IBD. Risk of CRC assessed as incidence proportion ("absolute risk," IP) and relative risk (RR). RESULTS: Familial CRC was associated with a more than 2-fold risk of CRC (adjusted RR = 2.5, 95% confidence interval 1.4-4.4) and an increase in the IP of CRC at 54 years of age from 3.8% to 6.9%. Patients with a first-degree relative diagnosed with CRC before 50 years of age had a higher RR (9.2, 95% confidence interval 3.7-23) and the highest IP (29%). No association with familial IBD was observed. CONCLUSIONS: Information on family history of CRC may be a simple way to identify individuals with IBD at elevated risk of developing CRC.     

The comorbid occurrence of other diagnoses in patients with ulcerative colitis and Crohn's disease

OBJECTIVES: The comorbidity between inflammatory bowel disease (IBD) and other diagnoses may help to shed light on the etiology and pathophysiology of IBD. The US Vital Statistics offer the opportunity to study causes of death broken down by comorbid disease associations. The aim of this study was to analyze the presence of comorbid conditions in persons who died from ulcerative colitis or Crohn's disease. METHODS: The numbers of deaths from ulcerative colitis and Crohn's disease were retrieved from the computerized 1991-1996 data files of the National Center for Health Statistics. Comorbid associations between other diagnosis and ulcerative colitis or Crohn's disease were expressed as age-, gender-, and race-standardized proportional mortality ratios. RESULTS: Ulcerative colitis and Crohn's disease showed, in general, similar patterns of comorbidity. Both diseases were associated with similar sets of GI complications, such as intestinal obstruction and stasis, mucosal inflammation and infection, vascular complications, and complications related to fistula and abscess formation. Extraintestinal complications of both IBD involved disorders of the hepatobiliary system, urinary system, and various coagulopathies. Ulcerative colitis alone was found to be associated with Hirschsprung's disease and schizophrenia, whereas Crohn's disease alone was found to be related with osteoporosis and amyloidosis. CONCLUSIONS: No completely unexplained or hitherto undescribed association was revealed. The numerous intestinal and extraintestinal complications associated with IBD serve as a reminder of the systemic nature and the resultant clinical severity of both ulcerative colitis and Crohn's disease.     

Association between ulcerative colitis and multiple sclerosis

An association between inflammatory bowel disease (IBD) and multiple sclerosis (MS) has been described. The current study was undertaken to explore this association further. Personal records of patients with IBD and MS were reviewed. In addition, a search of medical records at a large tertiary teaching hospital in Sydney was carried out for the years 1996–2006. Four patients (three women and one man) with both ulcerative colitis and MS were identified. MS did not occur in any of our patients with Crohn's disease. The association between ulcerative colitis and MS appears to be real and may help identify common factors involved in the cause of these two diseases. No association was found in this study between MS and Crohn's disease, sparking consideration why such difference should occur. With the increasing use of biological therapies in IBD and their reported propensity to cause demyelination, recognition of an association is all the more important.     

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.     

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.     

Familial occurrence of inflammatory bowel disease in celiac disease

BACKGROUND: The authors have previously reported a possible increased risk of the familial occurrence of Crohn's disease in patients with celiac disease. AIM: The aim of the current study was to evaluate in a case-control study the familial occurrence of inflammatory bowel disease (IBD) in first-degree relatives of patients with celiac disease. METHODS: One hundred eleven consecutive patients with biopsy-proven celiac disease were interviewed to ascertain whether IBD was present in first-degree relatives. The number of relatives, their ages, and possible IBD status were collected in a questionnaire. When a diagnosis of familial IBD was reported, the diagnosis was checked in the hospital records. Two hundred twenty-two controls matched for age and sex (111 from the general population and 111 from orthopedic wards) were also interviewed regarding the possible occurrence of IBD in first-degree relatives. The chi2 test was used to evaluate the difference in proportion of familial occurrence of IBD among individuals with celiac disease and controls. RESULTS: Among 600 first-degree relatives of patients with celiac disease, 10 cases of IBD were identified among first-degree relatives (7 cases of ulcerative colitis and 3 cases of Crohn's disease), whereas only 1 case of IBD was identified among the 1,196 first-degree relatives of control patients (p < 0.01). When ulcerative colitis and Crohn's disease were analyzed separately, only the prevalence of ulcerative colitis was statistically significant (p 相似文献   

细胞毒性T淋巴细胞相关抗原4基因微卫星多态性与炎症性肠病的关系

目的探讨细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因微卫星多态性与浙江省炎症性肠病（IBD）患者的相关性。方法对118例无血缘关系的IBD患者（99例溃疡性结肠炎，19例克罗恩病）以及140例正常对照者，采用特异性等位基因PCR方法，检测CTLA-4外显子4的3′非翻译区包含（AT）。重复序列的等位基因。扩增产物用12％非变性聚丙烯酰胺凝胶电泳，硝酸银染色。结果CTLA-4微卫星共有20种等位基因。与正常对照组比较，122bp等位基因频率在溃疡性结肠炎患者（P=0.0001／Pc=0．0025，OR=11.393，95％CI：2．574～50．429）和克罗恩病患者（P=0．0003／Pc=0.0050，OR=21.061，95％CI：3，927～112．94）中均显著增高。结论CTLA-4基因微卫星多态性与浙江省IBD患者显著相关。     

Inflammatory bowel disease in patients with celiac disease

BACKGROUND: Several case reports and series report an association between celiac disease and inflammatory bowel disease (IBD); however, there is no current data assessing this association. We therefore studied the occurrence of these conditions in a cohort of patients with celiac disease seen at a referral center. METHODS: A database of patients with celiac disease seen between 1981 and 2002 was analyzed. Only biopsy-proven adults were included. Patients who had endoscopic and pathologic evidence of IBD were identified, and their pathology was reviewed. Age- and sex-adjusted prevalence rate ratios were determined by comparing results with population-based prevalence data. RESULTS: Among 455 patients with celiac disease, IBD was identified in 10 (5 had ulcerative colitis and 5 had Crohn's disease). This represented an age- and sex-adjusted prevalence rate ratio for ulcerative colitis of 3.56 (95% confidence interval, 1.48-8.56) and for Crohn's disease of 8.49 (95% confidence interval, 3.53-20.42). CONCLUSION: Within our cohort of patients with celiac disease, IBD was significantly more common than in the general population.