Cytokine gene polymorphisms and genetic association with coeliac disease in the Finnish population.
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.
Woolley
N
N
Research Laboratory and Department of Tissue Typing, Finnish Red Cross Blood Service, Helsinki, Finland. jukka.partanen@bts.redcross.fi
Mustalahti
K
K
Mäki
M
M
Partanen
J
J
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
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