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Article Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease. 2008
Kugathasan S, Baldassano RN, Bradfield JP, Sleiman PM, Imielinski M, Guthery SL, Cucchiara S, Kim CE, Frackelton EC, Annaiah K, Glessner JT, Santa E, Willson T, Eckert AW, Bonkowski E, Shaner JL, Smith RM, Otieno FG, Peterson N, Abrams DJ, Chiavacci RM, Grundmeier R, Mamula P, Tomer G, Piccoli DA, Monos DS, Annese V, Denson LA, Grant SF, Hakonarson H. · Department of Pediatrics, Children's Research Institute and Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. · Nat Genet. · Pubmed #18758464 No free full text.
Abstract: Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn's disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 x 10(-8) and 6.95 x 10(-8), respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 x 10(-8); OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.
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Article US estimates of hospitalized pediatric patients with ulcerative colitis: implications for multicenter clinical studies. 2008
Guthery SL, Dong L, Dean JM, Holubkov R. · Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA. · Inflamm Bowel Dis. · Pubmed #18512244 No free full text.
Abstract: BACKGROUND: The optimal clinical management of children hospitalized with ulcerative colitis (UC) is evolving. There are limited data quantifying the number of pediatric patients with UC admitted to hospitals in the United States. We analyzed the Kids' Inpatient Database (KID, 2003), to estimate the distribution of hospitalized children with UC and estimate sample sizes available for clinical research. METHODS: We limited our analysis to subjects age less than 18 years. We defined cases of UC as discharge records associated with an ICD-9 code of 556.0-556.9 in the first position. We defined colectomy as principal procedure code of 45.8. We generated weighted estimates for these analyses. To estimate the relationship between number of patients and number of hospitals necessary for clinical trials, we generated 1000 simulated datasets. RESULTS: A total of 2311 UC cases were identified. The mean age at admission was 13.1 (standard error [SE] 0.1) years, and 9% (SE 0.9%) underwent colectomy during their hospitalization. 1008 UC cases were treated at high-volume hospitals; the majority of these children were treated at children's hospitals. Simulation studies suggest that approximately 5 high-volume hospitals would be necessary to generate sample sizes necessary for a pilot clinical trial of refractory UC. CONCLUSIONS: Approximately half of all young patients hospitalized with UC in the US were treated at a limited number of high-volume hospitals, and approximately 5 such centers would be adequate for pilot clinical trials of hospitalized patients with refractory UC.
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