Postinfectious Irritable Bowel Syndrome

https://www.gastrojournal.org/article/S0016-5085(03)00157-4/pdf

Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms

Behcet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production.

Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease

In this review, we consider the motivation behind contemporary single nucleotide polymorphism (SNP) initiatives. Many of these initiatives are projected to involve large, population-based surveys. We therefore emphasize the utility of SNPs for genetic epidemiology studies. We start by offering an overview of genetic polymorphism and discuss the historical use of polymorphism in the identification of disease-predisposing genes via meiotic mapping. We next consider some of the unique aspects of SNPs, and their relative advantages and disadvantages in human population-based analyses. In this context, we describe and critique the following six different areas of application for SNP technologies: Gene discovery and mapping. Association-based candidate polymorphism testing. Diagnostics and risk profiling. Prediction of response to environmental stimuli, xenobiotics and diet. Homogeneity testing and epidemiological study design. Physiologic genomics. We focus on key issues within each of these areas in an effort to point out potential problems that might plague the use of SNPs (or other forms of polymorphism) within them. However, we make no claim that our list of considerations are exhaustive. Rather, we believe that they may provide a starting point for further dialog about the ultimate utility of SNP technologies. In addition, although our emphasis is placed on applications of SNPs to the understanding of human phenotypes, we acknowledge that SNP maps and technologies applied to other species (e.g. the mouse genome, pathogen genomes, plant genomes, etc.) are also of tremendous interest.

Single nucleotide polymorphisms and the future of genetic epidemiology

Background Polymorphisms in cytokine genes can influence immune responses, inflammation, and tissue injury and may affect the outcome of hematopoietic stem-cell transplantation. Methods We analyzed single-nucleotide polymorphisms in the genes for interleukin-1β, interleukin-1–receptor antagonist, interleukin-6, interleukin-10 (IL10), and tumor necrosis factor α in 570 transplant recipients and their HLA-identical sibling donors. Genotypes were tested for an association with graft-versus-host disease (GVHD) by multivariable analysis. A second cohort of 423 transplant recipients was independently analyzed for the genotype associations identified in the first cohort. Results The recipient's IL10 promoter region genotype was significantly associated with the risk of acute GVHD in the first cohort. Analysis of all 993 transplant recipients showed that, as compared with the C/C genotype, the IL10 –592A/A genotype was associated with a decreased risk of grade III or IV acute GVHD (hazard ratio, 0.4; 95 percent c...

/pdf/relation-of-an-interleukin-10-promoter-polymorphism-to-graft-3nqwd892ee.pdf

Relation of an Interleukin-10 Promoter Polymorphism to Graft-versus-Host Disease and Survival after Hematopoietic-Cell Transplantation

Objective. To determine the distribution of the interleukin-10 (IL-10) 5' flanking region haplotypes in children with arthritis and in controls, and to investigate the functional significance of each haplotype. Methods. Sequence-specific oligonucleotide probing was used to determine haplotype frequency. Transient transfection studies were used to investigate the transcription of reporter genes driven by each haplotype. Whole blood cultures were performed to assess IL-10 production by each genotype. Results. Patients with arthritis involving >4 joints were more likely to have a genotype with an ATA haplotype than those whose arthritis remained restricted to <4 joints. This ATA haplotype was associated with lower transcriptional activity than the GCC haplotype (P = 0.02), and the ATA/ATA genotype was associated with lower IL-10 production under lipopolysaccharide stimulation than other genotypes (P < 0.02). Conclusion. The results of this study demonstrate the functional significance of the ATA haplotype and reveal a significant association of genotypes containing this haplotype with extended oligoarthritis.

Polymorphic haplotypes of the interleukin‐10 5′ flanking region determine variable interleukin‐10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis

Pritash Patel

Papers

Polymorphic haplotypes of the interleukin‐10 5′ flanking region determine variable interleukin‐10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis