Analysis of the risk factors and their combinations in acute gastroduodenal ulcer bleeding: a case-control study.

OBJECTIVE: Traditional non-steroidal anti-inflammatory drugs (NSAIDs) including ASA for thrombosis prophylaxis (ASA-TP), for pain medication (ASA-P) or non-ASA NSAIDs (NANSAIDs), Helicobacter pylori infection, CagA strains of H. pylori and smoking are reported risk factors for peptic ulcer bleeding (PUB), but the combined and the dose effects of these factors are controversial. The aim of this study was to estimate the significance of these risk factors and their combinations in PUB. MATERIAL AND METHODS: PUB patients (n = 94) were compared with an age- (+/- 5 years) and gender-matched control group of non-ulcer patients (n = 94) attending elective endoscopy. A questionnaire on the possible risk factors (previous gastric and duodenal ulcer, use of ASA-TP, ASA-P, NANSAIDs, warfarin, alcohol and smoking) was completed. H. pylori infection was determined as positive if histology and/or urease tests were positive. CagA antibodies of IgG class were determined using an immunoblot method. RESULTS: H. pylori infection (odds ratio (OR) 8.8), the use of ASA-P (OR 3.5), ASA-TP (OR 4.07), NANSAIDs with > or =1 defined daily dose (OR 6.56), smoking > or =20 cigarettes daily (OR 6.43) and previous duodenal ulcer (DU) (OR 8.96) were independent risk factors for PUB. At least two risk factors were present in 65% of PUB patients. CagA strains were detected in 97% of the H. pylori-positive cases and in 96% of the respective controls. ASA, ibuprofen, ketoprofen and smoking were dose-dependent risk factors for PUB. CONCLUSIONS: Previous DU, H. pylori, the use of any ASA and smoking explained the majority of the PUB episodes. CagA strains of H. pylori were not associated with PUB. Two-thirds of the PUB patients had at least two risk factors, but their combination did not potentiate the risk.

No observed local immunological response at cell level after five years of oats in adult coeliac disease.

OBJECTIVE: Our earlier 5-year follow-up study produced the first evidence to show the long-term safety of oats as part of a coeliac diet. The objective of the present study was to clarify its applicability by analysing local cellular immunological responses after 5 years' consumption of oats by adult coeliac patients. MATERIAL AND METHODS: Forty-two coeliac patients took part in an earlier oats intervention study for 6-12 months. Twenty-two of these patients originally consumed oats as part of their gluten-free diet. During the 5-year follow-up 10 patients had felt uncertain about the safety of long-term consumption of oats and gave up this part of their diet. Finally, 12 of the 22 patients consumed oats for the whole 5-year period. The control group consisted of the remaining 20 coeliac patients using a strict, conventional, gluten-free diet without oats. Intraepithelial CD3, alphabetaTCR (alphabetaIEL) and gammadeltaTCR (gammadeltaIEL) T cells were counted after specific staining of small intestinal biopsy specimens. RESULTS: There were no differences in the densities of CD3, alphabetaIEL and gammadeltaIEL T cells between the oat and the control groups. CONCLUSIONS: Long-term use of oats included in the gluten-free diets of patients with coeliac disease does not stimulate an immunological response locally in the mucosa of the small intestine.

HLA genotyping is useful in the evaluation of the risk for coeliac disease in the 1st-degree relatives of patients with coeliac disease.

OBJECTIVE: Coeliac disease (CD) is a common disease with a strong heredity. About 10-20% of 1st-degree relatives of probands develop CD. Relatives should be screened for CD, because if not treated, CD exposes patients to numerous complications. The heterogeneity of symptoms and the lifetime-spanning risk of CD render the timing of CD antibody and/or gastroscopy screenings difficult. As CD susceptibility has been shown to be strongly associated with the HLA alleles DQA1*0501 and DQB1*0201 (together encoding the DQ2 heterodimer) and DRB1*04 (associated with the DQ8 heterodimer), our aim was to investigate whether HLA genotyping might be useful in the identification of 1st-degree relatives of CD patients who do not need further screening for CD. MATERIAL AND METHODS: The study comprised 54 Finnish CD families including 54 CD probands and 382 living 1st-degree relatives. All subjects who were willing to participate were screened for CD (duodenal and skin biopsies; endomysial, reticulin and gliadin antibodies). The DQA1*0501, DQB1*0201 and DRB1*04 allele frequencies of CD patients and the 1st-degree relatives were determined. RESULTS: Altogether 17.6% (5.9% of the parents, 15.7% of the siblings, 25.8% of the offspring) of the investigated 1st-degree relatives (n = 245) did not carry any of the alleles studied. All of the CD patients (n = 136) with the exception of one (0.7%) carried at least one of the alleles investigated. CONCLUSIONS: By using the HLA genotyping a considerable proportion of 1st-degree relatives of CD probands could be excluded from further screening for CD.

Gene dose effect of the DQB1*0201 allele contributes to severity of coeliac disease.

OBJECTIVE: Coeliac disease (CD) susceptibility has been shown to be associated with the HLA alleles DQA1*0501 and DQB1*0201. This HLA-associated risk has been estimated to account for 29-40% of the genetic component of CD. Conflicting data have been published on the gene dose effect of these HLA alleles on the risk and severity of CD. In this study the aim was to investigate the association between the number of HLA risk alleles and the severity of CD. MATERIAL AND METHODS: Fifty-four Finnish CD families, including 144 CD patients mainly diagnosed in adulthood (94.4%), were enrolled in the study. The association between the number of DQA1*0501 and DQB1*0201 alleles and villous atrophy, symptoms and laboratory parameters at the time of diagnosis, and the association with villous atrophy after one year of treatment on a gluten-free diet were studied. RESULTS: The homozygosity for the DQB1*0201 allele was associated with a more severe form of CD assessed by more severe villous atrophy (p=0.011), younger age (p=0.036), more severe diarrhoea (p=0.048) and a lower level of blood haemoglobin at the time of diagnosis (p=0.010). Furthermore, the homozygosity for the DQB1*0201 allele was associated with a slower recovery of villous atrophy after a gluten-free diet (p=0.041). In contrast, the DQA1*0501 allele did not have a significant association with the severity of CD. CONCLUSIONS: Our results demonstrate a gene dose effect of the DQB1*0201 allele on the clinical heterogeneity of CD and on the rate of recovery from villous atrophy in patients on a gluten-free diet.

Genomewide search and association studies in a Finnish celiac disease population: Identification of a novel locus and replication of the HLA and CTLA4 loci.

It has been reported that celiac disease (CD) is strongly associated with the HLA-DQ2 alleles DQA1*0501 and DQB1*0201. However, this association only accounts for a portion of the genetic component of CD. Several non-HLA loci and candidate genes that potentially contribute to CD susceptibility have been reported, but have not been confirmed. The aim of this study was to identify loci that contribute to disease susceptibility in a CD population from Finland. We performed a genomewide linkage scan and identified two regions of significant linkage to CD (6p and 2q23-32) and one region of suggestive linkage (10p). We also performed targeted typing and analyses that replicated the associations of the HLA and CTLA4 loci.