Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms.

Background: The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.

Genetic analysis of innate immunity in Crohn's disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP.

The two main phenotypes of inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--are chronic intestinal inflammatory disorders with a complex genetic background. Using a three-stage design, we performed a functional candidate-gene analysis of innate immune pathway in IBD. In phase I, we typed 354 SNPs from 85 innate immunity genes in 520 Dutch IBD patients (284 CD, 236 UC) and 808 controls.

The MYO9B gene is a strong risk factor for developing refractory celiac disease.

Background & Aims: Celiac disease (CD) is associated with HLA-DQ2 and HLA-DQ8 and has been linked to genetic variants in the MYO9B gene on chromosome 19. HLA-DQ2 homozygosity is associated with complications of CD such as refractory celiac disease type II (RCD II) and enteropathy-associated T-cell lymphoma (EATL). We investigated whether MYO9B also predisposes to RCD II and EATL.

Is MYO9B the missing link between schizophrenia and celiac disease?

There has long been discussion on the correlation between schizophrenia and autoimmune diseases (especially celiac disease), which makes the recently discovered celiac disease risk factor, MYO9B, an attractive functional and positional candidate gene for schizophrenia. To test this hypothesis we compared allele frequencies of three MYO9B tag SNPs in 315 schizophrenia cases and 1,624 healthy controls in a genetic association study. Highly significant differences in allele frequencies between schizophrenia cases and healthy controls were observed for SNP rs2305767 in intron 14 of MYO9B (P = 1.

Understanding the molecular basis of celiac disease: what genetic studies reveal.

Celiac disease (CD) is characterized by a chronic immune reaction in the small intestine to the gluten proteins that are present in a (Western) daily diet. Besides the well known involvement of the HLA class II histocompatibility antigen (HLA)-DQ2.5 and -DQ8 heterodimers (encoded by particular combinations of the HLA-DQA1 and -DQB1 gene) in CD and the minor contribution of the CTLA-4 gene, recently the myosin IXB (MYO9B) gene has also been found to be genetically associated.

The SPINK gene family and celiac disease susceptibility.

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was determined for all four SPINK genes by quantitative reverse-transcription polymerase chain reaction in duodenal biopsy samples from untreated (n=15) and diet-treated patients (n=31) and controls (n=16).

Genetic variation in myosin IXB is associated with ulcerative colitis.

Background & Aims: Common germline genetic variation in the 3' region of myosin IXB (MYO9B) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease.

Methods: Eight single-nucleotide polymorphisms (SNPs) were selected to tag common haplotypes from the 35-kb 3' region of MYO9B.

A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC.

The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC.

A functional candidate screen for coeliac disease genes.

It is increasingly evident that different inflammatory disorders show some overlap in their pathological features, concurrence in families and individuals, and shared genetic factors. This might also be true for coeliac disease, a chronic inflammatory disorder of the gastrointestinal system, which shares two linkage regions with inflammatory bowel disease: on chromosome 5q31 (CELIAC2 and IBD5) and 19p13 (CELIAC4 and IBD6). We hypothesised that these regions contain genes that contribute to susceptibility to both disorders.

The downstream modulator of interferon-gamma, STAT1 is not genetically associated to the Dutch coeliac disease population.

Coeliac disease (CD) is a complex genetic disorder. Its etiology is owing to multiple genes and environmental factors, such as gluten. The first event in the pathogenesis of CD after the ingestion of gluten is the activation of a Th1 immune response that leads to villous atrophy.

Association analysis of MYO9B gene polymorphisms with celiac disease in a Swedish/Norwegian cohort.

Association between myosin IXB (MYO9B) gene variants and celiac disease (CD) has been reported in a study of a Dutch cohort. Six single nucleotide polymorphisms (SNPs) within the 3' part of the MYO9B gene showed significant genetic association and formed an associated haplotype. The current study aimed to replicate these findings in a Swedish/Norwegian cohort.

Genetic and functional analysis of pyroglutamyl-peptidase I in coeliac disease.

Coeliac disease (CD) is an enteropathy caused by an immune reaction towards wheat gluten and similar proteins from barley and rye. It was shown that some gluten peptides spontaneously form N-terminal L-pyroglutamate. This modification could potentially make gluten more resistant to proteolytic degradation within the intestine.

Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect.

Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified.

No genetic association of the human prolyl endopeptidase gene in the Dutch celiac disease population.

Celiac disease (CD) is a complex genetic disorder of the small intestine. The DQ2/DQ8 human leucocyte antigen (HLA) genes explain approximately 40% of the genetic component of the disease, but the remaining non-HLA genes have not yet been identified. The key environmental factor known to be involved in the disease is gluten, a major protein present in wheat, barley, and rye.