title: Cytokine gene polymorphisms and genetic association with coeliac disease in the Finnish population.
abstract: Coeliac disease (CD) is an intestinal disorder caused by intolerance to dietary gluten in susceptible individuals. The HLA-DQ genes are major risk factors for CD, but other genes also play an important role in the disease susceptibility. Immune-mediated mechanisms are known to underlie the pathogenesis of CD. We studied single-nucleotide polymorphisms in transforming growth factor (TGF)-beta1, interleukin (IL)-10, IL-6, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha genes in the Finnish population using family-based association approach. In addition, we genotyped a trinucleotide repeat polymorphism in the major histocompatibility complex (MHC) class I chain-related protein A (MICA) gene, located in the human leucocyte antigen (HLA) region in the vicinity of TNF-alpha. To control the effect of linkage disequilibrium between HLA-DQ genes and MICA and TNF-alpha, an HLA-stratified association analysis was performed. We did not find evidence of association between TGF-beta1, IL-10, IL-6 and IFN-gamma polymorphisms and CD susceptibility. No association was found for any of the MICA alleles independently of DQ genes, whereas TNF-alpha-308 A allele was slightly overrepresented on chromosomes carried by CD patients compared with control chromosomes, indicating that either TNF-alpha, or another gene in linkage disequilibrium with it, could confer increased susceptibility to CD. This result supports the earlier findings that the HLA region harbours a novel susceptibility factor in addition to HLA-DQ.
authors.affiliation: Research Laboratory and Department of Tissue Typing, Finnish Red Cross Blood Service, Helsinki, Finland. jukka.partanen@bts.redcross.fi
authors.forename: N
authors.initials: N
authors.lastname: Woolley
authors.forename: K
authors.initials: K
authors.lastname: Mustalahti
authors.forename: M
authors.initials: M
authors.lastname: Mäki
authors.forename: J
authors.initials: J
authors.lastname: Partanen
mesh_terms: D000483:Alleles; D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005387:Finland; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D018911:Trinucleotide Repeats; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D006683:HLA-DQ Antigens; D015395:Histocompatibility Antigens Class I; D015850:Interleukin-6; C099187:MHC class I-related chain A; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma