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| 2. |
- Angsten, Gertrud, et al.
(author)
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Improved outcome in neonatal short bowel syndrome using parenteral fish oil in combination With ω-6/9 Lipid Emulsions
- 2012
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In: JPEN - Journal of Parenteral and Enteral Nutrition. - : Wiley. - 0148-6071 .- 1941-2444. ; 36:5, s. 587-595
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Journal article (peer-reviewed)abstract
- Background:Newborn infants with short bowel syndrome (SBS) represent a high risk group of developing intestinal failure-associated liver disease (IFALD) which may be fatal. However, infants have a great capacity for intestinal growth and adaptation if IFALD can be prevented or reversed. A major contributing factor to IFALD may be the soybean oil-based intravenous lipid emulsions used since the introduction of parenteral nutrition (PN) 40 years ago. Methods:This retrospective study compares the outcome in 20 neonates with SBS treated with parenteral fish oil (Omegaven) in combination with omega-6/9 lipid emulsions (ClinOleic) with the outcome in a historical cohort of 18 patients with SBS who received a soybean oil-based intravenous lipid emulsion (Intralipid).Results:Median gestational age was 26 weeks in the treatment group and 35.5 weeks in the historical group. All patients were started on PN containing Intralipid that was switched to ClinOleic/Omegaven in the treatment group at a median age of 39 gestational weeks. In the treatment group, direct bilirubin levels were reversed in all 14 survivors with cholestasis (direct bilirubin >50 umol/). Median time to reversal was 2.9 months. Only 2 patients died of liver failure (10%). In the historical cohort, 6 patients (33%) died of liver failure and only 2 patients showed normalization of bilirubin levels.Conclusions:Parenteral fish oil in combination with omega-6/9 lipid emulsions was associated with improved outcome in premature neonates with SBS. When used instead of traditional soybean-based emulsions, this mixed lipid emulsion may facilitate intestinal adaptation by increasing the IFALD-free period.
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| 6. |
- Engstrand Lilja, Helene, 1963-, et al.
(author)
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Intestinal dysbiosis in children with short bowel syndrome is associated with impaired outcome
- 2015
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In: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 3
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Journal article (peer-reviewed)abstract
- Background: The composition of the intestinal microbiota seems to be an important factor in determining the clinical outcome in children with short bowel syndrome (SBS). Alterations in the microbiota may result in serious complications such as small bowel bacterial overgrowth (SBBO) and intestinal mucosal inflammation that lead to prolonged parenteral nutrition (PN) dependency with subsequently increased risk of liver failure and sepsis. To date, there are no reported mappings of the intestinal microbiome in children with SBS. Here, we present the first report on the intestinal microbial community profile in children with SBS. Findings: The study includes children diagnosed with SBS in the neonatal period. Healthy siblings served as controls. Fecal samples were collected, and microbial profiles were analyzed by using 16S rRNA gene sequencing on the Illumina MiSeq platform. We observed a pronounced microbial dysbiosis in children with SBS on PN treatment with an increased and totally dominating relative abundance of Enterobacteriacae in four out of five children compared to children with SBS weaned from PN and healthy siblings. Conclusions: The overall decreased bacterial diversity in children with SBS is consistent with intestinal microbiome mappings in inflammatory bowel diseases such as Crohn's disease and necrotizing enterocolitis in preterm infants. Our findings indicate that intestinal dysbiosis in children with SBS is associated with prolonged PN dependency.
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| 11. |
- Fredriksson, Fanny, 1985-, et al.
(author)
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Improved Outcome of Intestinal Failure in Preterm Infants
- 2020
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In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Wolters Kluwer. - 0277-2116 .- 1536-4801. ; 71:2, s. 223-231
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The aims were to evaluate the outcome and to identify predictors for survival and enteral autonomy in neonatal intestinal failure (IF).METHODS: A retrospective observational study in a Swedish tertiary centre of children born between 1995 and 2016 with neonatal IF, defined as dependency on parenteral nutrition (PN) ≥60 days, starting with PN before the age of 44 gestational weeks. Data were extracted from medical records and predictors for survival and enteral autonomy were identified by the Cox regression model. Time to death and weaning off PN analysis were performed with Kaplan-Meier curves including log rank test.RESULTS: In total, 105 children were included. Median gestational age was 28 weeks (22-42), 50% were born extremely preterm (<28 gestational weeks). PN started at a median age of two days (0-147) with a median duration of 196 days (60-3091). Necrotising enterocolitis was the dominating cause of IF (61%). Overall survival was 88%, five children died of sepsis and four of intestinal failure-associated liver disease. Survival increased from 75% during 1995-2008 to 96% during 2009-2016 (p = 0.0040). Age-adjusted small bowel length of >50% and birth 2009-2016 were predictors for survival. Enteral autonomy was achieved in 87%, with positive prediction by small bowel length of >25% of expected for gestational age and remaining ileocaecal valve.CONCLUSION: Preterm neonates with IF, at high risk of IF associated morbidity, showed a high overall survival rate. Small-bowel length and being born 2009-2016 were predictors for survival and remaining ICV and small-bowel length were predictors for enteral autonomy.
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| 12. |
- Herlenius, Gustaf, et al.
(author)
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Tarmtransplantation : experimentell terapi som blivit realistiskt alternativ
- 2004
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:38, s. 2874-2878
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Journal article (peer-reviewed)abstract
- Outcome after intestinal transplantation has improved dramatically since the introduction of novel immunosuppressive agents and refined surgical techniques. Small bowel transplantation is now considered to be the best treatment modality for patients with life threatening complications of intestinal failure and parenteral nutrition. We hereby review the international experience as well as the first ten cases of intestinal transplantation performed in Sweden.
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| 13. |
- Ideström, Maja, et al.
(author)
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Pediatric Crohn's disease from onset to adulthood : granulomas are associated with an early need for immunomodulation
- 2014
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 49:8, s. 950-7
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Childhood onset Crohn's disease (CD) is considered more aggressive than adult onset disease. Epithelioid cell granulomas in intestinal biopsies are one, non-obligate, criterion of CD. We investigated granulomas as markers of CD severity in children followed to adulthood.MATERIAL AND METHODS: Forty-five individuals with childhood onset CD were studied from diagnosis until attainment of final height, with data on disease location, medical and surgical management and with detailed growth data analyses. A blinded review of diagnostic biopsies was also performed.RESULTS: We found granulomas in 22/45 (49%) children at diagnosis, altogether in 28/45 (62%) patients during the disease course (median overall follow-up - 12.3 years, range 9.3-18). Granulomas were found in 9/11 (82%) with upper gastrointestinal involvement (cumulatively 17/20, 85%) (p = 0.017 and p = 0.006, respectively). The time from diagnosis to initiating immune modulating treatment (median 4.5 months, range 0-75) was shorter in the granuloma-positive group (16/22) compared to the granuloma-negative group (18/23) (median 33 months, range 2-105; p = 0.01). The median standard deviation score height at diagnosis and final adult height (both adjusted for target height) did not correlate to findings of granulomas.CONCLUSIONS: Epithelioid cell granulomas were associated with a shorter time to initiating immune modulating drugs, as a possible sign of more severe disease, but growth was not affected.
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| 14. |
- Lilja, Helene Engstrand, et al.
(author)
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Prevention and reversal of intestinal failure-associated liver disease in premature infants with short bowel syndrome using intravenous fish oil in combination with omega-6/9 lipid emulsions
- 2011
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In: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 46:7, s. 1361-1367
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Journal article (peer-reviewed)abstract
- Although premature infants with short bowel syndrome are at the highest risk of developing intestinal failure-associated liver disease (IFALD), they have great capacity for intestinal growth and adaptation if IFALD can be prevented. Conventional soybean oil-based intravenous lipid emulsions have been associated with IFALD. This study presents data on 5 premature neonates with short bowel syndrome treated with a combination of parenteral fish oil-and olive/soybean-based lipid emulsion for periods ranging between 7 and 17 months. Despite an enteral tolerance of less than 50% in 4 of these patients during their first year of life, direct bilirubin levels normalized while on this combination of ClinOleic (Baxter, Maurepas, France)/Omegaven (Fresenius Kabi, Bad Homburg, Germany) at a 1: 1 ratio. None of our patients developed irreversible IFALD even though all of them were premature, had undergone multiple major surgical procedures, and had experienced several episodes of sepsis. Thus far, we have not seen any adverse effects of this mixed lipid emulsion in these preterm infants. All 5 patients are growing and developing well and have normal liver function.
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| 15. |
- Lorentzon Fagerberg, Ulrika, et al.
(author)
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Fecal calprotectin : a quantitative marker of colonic inflammation in children with inflammatory bowel disease
- 2007
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In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 45:4, s. 414-420
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Journal article (peer-reviewed)abstract
- Objectives: The protein calprotectin (S100 A8/A9) is present in neutrophils, monocytes, and macrophages. Colorectal inflammation can be detected by increased excretion of fecal calprotectin (FC). The aim of this study was to evaluate FC as a quantitative marker of inflammatory activity in children with inflammatory bowel disease (IBD). Patients and Methods: Thirty-nine children with IBD delivered a fecal spot sample and underwent colonoscopy. The samples were examined with an enzyme-linked immunosorbent assay for FC (Calprest, Eurospital, Trieste, Italy). The concentrations were correlated to macroscopic and microscopic assessments of extent and severity of inflammation in 8 colonic segments for each patient. Results: FC correlated significantly to the macroscopic extent (Spearman p=0.61) and the severity (Spearman p=0.52) of colonic inflammation and to a macroscopic, combined extent and severity score (Spearman p = 0.65). Significant correlations also were found to the microscopic extent (Spearman p=0.71) and severity (Spearman p = 0.72) of colonic inflammation and to a microscopic, combined extent and severity score (Spearman p=0.75). The median FC was 392 μg/g (95% confidence interval [CI], 278-440) in children with clinical IBD symptoms (n=23) and 32.9 μg/g (95% CI, 9.4-237) in asymptomatic IBD patients (n= 16). Of the asymptomatic children, 56% had a complete microscopic mucosal healing, and their median FC was 9.9 μg/g (95% CI, 5.9-41.9). Conclusions: FC can be used as a surrogate marker for estimation of colonic inflammation in pediatric IBD. Normalized FC concentration seems to indicate complete mucosal healing. FC is simple to obtain and analyze; this should facilitate objective assessment and monitoring of IBD activity.
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| 16. |
- Momozawa, Yukihide, et al.
(author)
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Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease
- 2011
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In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 43:1, s. 43-47
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ∼20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease.
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| 17. |
- Nyström, Niklas, et al.
(author)
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Human Enterovirus Species B in Ileocecal Crohn's Disease
- 2013
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In: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 4:6
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Advanced ileocecal Crohn's disease (ICD) is characterized by strictures, inflammation in the enteric nervous system (myenteric plexitis), and a high frequency ofNOD2mutations. Recent findings implicate a role ofNOD2and another CD susceptibility gene,ATG16L1, in the host response against single-stranded RNA (ssRNA) viruses. However, the role of viruses in CD is unknown. We hypothesized that human enterovirus species B (HEV-B), which are ssRNA viruses with dual tropism both for the intestinal epithelium and the nervous system, could play a role in ICD.METHODS:We used immunohistochemistry andin situhybridization to study the general presence of HEV-B and the presence of the two HEV-B subspecies, Coxsackie B virus (CBV) and Echovirus, in ileocecal resections from 9 children with advanced, stricturing ICD and 6 patients with volvulus, and in intestinal biopsies from 15 CD patients at the time of diagnosis.RESULTS:All patients with ICD had disease-associated polymorphisms inNOD2orATG16L1. Positive staining for HEV-B was detected both in the mucosa and in myenteric nerve ganglia in all ICD patients, but in none of the volvulus patients. Expression of the cellular receptor for CBV, CAR, was detected in nerve cell ganglia.CONCLUSIONS:The common presence of HEV-B in the mucosa and enteric nervous system of ICD patients in this small cohort is a novel finding that warrants further investigation to analyze whether HEV-B has a role in disease onset or progress. The presence of CAR in myenteric nerve cell ganglia provides a possible route of entry for CBV into the enteric nervous system.
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| 18. |
- Nyström, Niklas
(author)
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Metabolomic features and viral infections in paediatric inflammatory bowel disease
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Background: Up to 25% of patients with inflammatory bowel disease have a paediatric onset (PIBD). The pathophysiological processes underlying PIBD are complex and largely unknown. Aims: To investigate a hypothesized role for human enterovirus B (HEV-B) in Crohn’s disease (CD) (I). To map and compare the mucosal and plasma metabolomes in new-onset PIBD patients and controls (II). To search for a new blood-based diagnostic biomarker for PIBD (III). To investigate the effect of exclusive enteral nutrition (EEN) treatment on the mucosal and plasma metabolomes in CD patients (IV). Methods: Immunohistochemistry and chromogen in situ hybridisation were used to search for HEV-B in surgical specimens from patients who had undergone surgery for stricturing ileocecal CD, and from volvulus patients as controls. Ultra-high-performance liquid chromatography mass spectrometry were used on biopsies and plasma from patients in the Uppsala PIBD inception cohort for metabolomic (II and IV) and lipidomic analyses (III). Patients were stratified by phenotypic subtypes and treatment responses. Symptomatic patients without PIBD were used as non-IBD controls. In Study III, two other independent PIBD inception cohorts were used for validation and confirmation. Results: I: HEV-B was detected in epithelial cells and neuronal ganglia of the enteric nervous system, and the specific cellular Coxsackie and adenovirus receptor (CAR) was expressed in both the intestinal epithelium and the enteric nervous system. II: Alterations in two metabolic compound classes were seen: decreased levels of lysophospholipids in inflamed ileum of CD patients and altered levels of sphingolipids in inflamed ileum and colon in both CD and ulcerative colitis, as compared with non-IBD controls. III: Discovery, validation and confirmation in three independent PIBD inception cohorts of a blood-based diagnostic two-lipid signature of PIBD. IV: A generalised downregulation of the non-inflamed ileal lipid metabolism after successful remission induction with EEN, as compared with baseline, and also as compared with non-IBD controls. Reduction of several lysophospholipids was a characteristic feature of the post-EEN ileal metabolome.Conclusions: The demonstrated presence of HEV-B supports, but does not confirm, its hypothesised role in CD. The CD-associated downregulation of mucosal metabolism both at disease onset and after successful EEN-induced inflammation resolution indicates a central role for the ileal mucosal lipid metabolism in CD, including lysophospholipids. The blood-based two-lipid signature has the potential of becoming a diagnostic tool in the clinical work-up of suspected PIBD.
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| 19. |
- Rolandsdotter, Helena, et al.
(author)
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Exclusive Enteral Nutrition : Clinical Effects and Changes in Mucosal Cytokine Profile in Pediatric New Inflammatory Bowel Disease
- 2019
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In: Nutrients. - : MDPI. - 2072-6643. ; 11:2
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Journal article (peer-reviewed)abstract
- Exclusive Enteral Nutrition (EEN) is the first-line treatment in children with Crohn's disease (CD) for induction of remission. However, the mode of action remains conjectural. The aim of this study was to investigate whether the effect of EEN is paralleled by changes in the mucosal cytokine profiles (MCP). Twelve children with new onset inflammatory bowel disease (IBD) received induction treatment with a polymeric EEN. We assessed clinical, endoscopic and histologic scoring before and after EEN. Twelve colonic cytokines were analyzed by Polymerase Chain Reaction (PCR) in six of the IBD patients at onset and after EEN as well as in six non-IBD control children at the diagnostic colonoscopy. Twelve children completed 6 weeks of EEN, except from one child who completed 4 weeks. At the control colonoscopy, 83% were in complete clinical remission. Changes were found in the MCPs of individual patients after EEN. In particular, children with IBD showed significantly higher values of Interleukin (IL)-12 (p = 0.008) and IL-23 (p = 0.02) compared to non-IBD controls at the diagnostic colonoscopy. Furthermore, an overall change in proinflammatory cytokines was noted in the IBD-group after treatment. Further studies are warranted to understand the role of EEN in MCP.
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| 20. |
- Rolandsdotter, Helena, et al.
(author)
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Granulocyte and Monocyte Apheresis for Induction of Remission in Children With New-Onset Inflammatory Bowel Colitis
- 2018
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In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 66:1, s. 84-89
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Journal article (peer-reviewed)abstract
- Objective: The aim of the study was to analyze the effect of granulocyte and monocyte apheresis (GMA) with mesalazine for induction of remission in pediatric patients with newly onset chronic inflammatory bowel disease (IBD) colitis.Methods: Thirteen pediatric patients with newly onset extensive IBD colitis were investigated per the ECCO/ESPGHAN IBD protocol. Of these 13, 12 received 10 treatments with Adacolumn (ADA) during a median of 6.25 weeks in combination with low-to-moderate doses of mesalazine, which was continued after apheresis. A control colonoscopy was performed 12 to 16 weeks after GMA treatment. Primary outcomes were mucosal healing (Mayo endoscopic score) and histopathologic grading of biopsies. A secondary outcome was disease activity as measured by the Pediatric Ulcerative Colitis Activity Index.Results: Twelve children (6 girls) with a median age of 14.6 years and a median duration of symptoms at diagnosis of 3.2 months received all planned 10 treatment sessions with ADA. Ten of 12 patients had pancolitis and 2 of 12 extensive colitis. A final diagnosis, however, indicated ulcerative colitis in 10 children and Crohn disease in 2 children. At control colonoscopy, 8 of 12 children were in clinical remission and the Mayo endoscopic score showed significant improvement in 9 of 12 patients (P = 0.006). Complete microscopic remission, according to the Geboes score, was observed in 2 patients.Conclusions: In this small study GMA for induction of remission of newly onset pediatric IBD colitis was effective in 8 of 12 patients. Further controlled studies are warranted to confirm the efficacy of this treatment model.
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| 21. |
- Rolandsdotter, Helena, et al.
(author)
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Mucosal Cytokine Profiles After Induction Therapy With Granulocyte/Monocyte Apheresis in New-onset Inflammatory Colitis
- 2018
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In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 66:4, s. E103-E107
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Journal article (peer-reviewed)abstract
- Granulocyte/monocyte apheresis (GMA) selectively removes circulating granulocytes and monocytes; important producers of proinflammatory cytokines. Seven children with new-onset inflammatory bowel disease (IBD) colitis were treated with GMA together with mesalazine, and had significant decreases in Pediatric UC Activity Index (P=0.018) and Mayo endoscopic score (P=0.013). We investigated the colonic mucosal cytokine profiles (analyzed with real-time polymerase chain reaction), before and after induction treatment, and in 6 non-IBD controls. Significant decreases were seen in Colony Stimulating Factor 2 (P=0.018), tumor necrosis factor- (P=0.028), interleukin (IL)-23 (P=0.043), IL-1 (P=0.028), IL-36 (P=0.018), IL-10 (P=0.028), and transforming growth factor beta 1 (P=0.043) after treatment. In 6 non-IBD controls there were significantly lower levels of IL-12 (P=0.023) and IL-23 (P=0.046) compared to the patients with IBD at onset, and IL-22 (P=0.088) and IL-36 (P=0.062) showed lower values without reaching significant differences. We speculate that the decreases in colonic mucosal cytokine profiles after treatment may explain the observed clinical efficacy in the GMA-treated children with IBD.
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| 22. |
- Skolin, Inger, 1949-
(author)
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Nutritional consequences in children undergoing chemotherapy for malignant disease
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Background: Chemotherapy has side effects that may interfere with food intake. Children suffering from a malignant disease are subjected to treatment with chemotherapy. They may therefore become at risk of undernutrition during the period of treatment. This in turn may increase the risk of infections, delayed therapy and influence the outcome of treatment. Few studies have investigated how children undergoing chemotherapy for cancer perceive food and eating. Attempts to improve food intake and the nutritional status require an understand-ing of how eating patterns are altered during chemotherapy in children. Study design: Dietary information and anthropometric data were collected after the initiation of chemotherapy in 14 children, consecutively admitted to the Paediatric Haematology and Oncology Unit at Umeå University Hospital. This initial study resulted in the establishment of more flexible mealtime routines on the ward. A follow-up study was conducted with another group of 11 children. Interviews were performed with a third group of 21 consecutively ad-mitted children, their parents and attending nurses. The focus was on the children’s own per-ception of and their parents’ and nurses’ attitudes to their food intake during hospitalisation. Recognition thresholds for the basic tastes were determined with 10 of the oldest of these children and 10 healthy controls. Results: Before introduction of new mealtime routines, the average daily oral energy intake during hospitalisation was 58% of the Swedish Nutrition Recommendations, SNR. The chil-dren had a significant weight loss up to three months after onset of chemotherapy. After the introduction of new mealtime routines, the average daily oral intake on hospital days was 61% of SNR and thus still lower than recommended despite efforts to serve palatable food on the ward. When enteral and parenteral nutrition was included, the energy intake came close to that recommended for healthy children, 91% of SNR. Both children and parents perceived that altered taste was an important cause of the children’s eating problems. The children also viewed food aversions, nausea and vomiting and pain as important causes, while the parents perceived nausea, food aversions and altered smell as significant factors. The nurses on the other hand, viewed nausea, the ward environment, and food rejection as a way of gaining some influence over the situation as important factors. The patients had significantly higher thresholds for bitter taste and significantly more patients made mistakes in taste recognition compared with controls. Conclusion and clinical implication: There seem to be changes both in the sense of taste as well as in the perception of food in children undergoing chemotherapy for malignant disease. Thus, single solutions such as providing a variety of “tasty food” in the hospital setting in order to improve food intake does not suffice for many paediatric cancer patients. The indi-vidual’s food preferences and aversions should be considered and combinations of oral, en-teral and parenteral nutrition support should be provided.
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| 23. |
- Soderman, Jan, et al.
(author)
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Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease
- 2013
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In: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 19:30, s. 4935-4943
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Journal article (peer-reviewed)abstract
- AIM: To investigate a possible genetic influence of claudin (CLDN) 1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn's disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease-families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing.RESULTS: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95% CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95% CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.
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