Chromosome 5q candidate genes in coeliac disease: Genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1

Abstract

Genetic predisposition to coeliac disease (CD) is determined primarily by alleles at the HLA-DQB locus, and evidence exists implicating other major histocompatibility complex-linked genes (6p21) and the CTLA4 locus on chromosome 2q33. In addition, extensive family studies have provided strong, reproducible evidence for a susceptibility locus on chromosome 5q (CELIAC2). However, the gene responsible has not been identified. We have assayed genetic variation at the IL4, IL5, IL9, IL13, IL17B and NR3C1 (GR) loci, all of which are present on chromosome 5q and have potential or demonstrated involvement in autoimmune and/or inflammatory disease, in a sample of 409 CD cases and 355 controls. Thirteen single nucleotide polymorphisms were chosen on the basis of functional relevance, prior disease association and, where possible, prior knowledge of the haplotype variation present in European populations. There were no statistically significant allele or haplotype frequency differences between cases and controls. Therefore, these results provide no evidence that these loci are associated with CD in this sample population.

Interleukin-6 and interleukin-17 gene polymorphism association with celiac disease in children

“…Previous studies have compared treated and potential patients with CD and have reported IL-17 elevation in the mucosa of untreated patients (14,15). However, Ryan et al (16) examined the relation between IL-17 polymorphisms and CD and showed no relation between IL-17 (762 C/A, 1586 A/G, and 6769 A/G) polymorphisms and CD. Espinoza et al (17) showed that the IL-17A 197A allele correlates to more efficient IL-17 production.…”

The severity of FIP1L1–PDGFRA-positive chronic eosinophilic leukaemia is associated with polymorphic variation at the IL5RA locus

“…[8][9][10][11][12] Such associations are postulated to be a consequence of natural variation in the expression levels of IL-5 or IL5RA and hence the strength of signalling through this pathway. In this study, we have investigated the hypothesis that genetic variation in IL-5 signalling may be associated with the development or severity of FIP1L1-PDGFRA-positive CEL in humans.…”

Advances in celiac disease

“…There has been no clear association with polymorphisms in many of these genes and celiac disease [24], apart from a significant increase in the frequency of the tumour necrosis factor a (TNF-a) À308A allele and the interferon (IFN-g) 874T allele with the two in combination in 40% versus 22% of controls [25]. A Finnish study [26 ] found no association with polymorphisms in interleukin (IL)-6, IL-10, transforming growth factor b (TGF-b) and IFN-g but an association of TNF-a À308A, although this was not statistically significant.…”