Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8644416 | Gene | 2018 | 6 Pages |
Abstract
Hirschsprung's disease (HSCR) is a congenital disease characterized by intestinal obstruction due to a defective intestinal neural system. Frequently, the disease is associated with an intestinal inflammation. The most common known underlying genetic alterations are in the RET gene but HSCR can also be caused by mutations in other genes that are responsible for the maturation and migration of intestinal neural cells. Recently, a study in an Asian population reported a significant association of several single nucleotide polymorphisms (SNPs) in the IL11 (interleukin 11) gene with HSCR. We further explored the possible association of genetic alterations in the IL11 gene with HSCR and HSCR subtypes in an unrelated Caucasian population. We used a targeted sequencing approach to identify a total of 32 SNPs covering the coding region of the IL11 gene including the proximal part of the promoter and relevant SNPs described in the previous study. Genotype frequencies were compared using additive genetic models in 103 HSCR patients and 128 healthy controls. We failed to observe any significant association of SNPs with HSCR. However, there was a suggestive evidence for an association of the length of a dinucleotide repeat in the IL11 promoter region with HSCR with an over-representation of >7 GT repeat subtypes (ORâ¯=â¯4.982 (1.448-17.040), p-valueâ¯=â¯0.0111) in HSCR patients. A similar trend was further observed in a subgroup of patients with long-segment HSCR (L-HSCR). These findings need to be replicated in a well-powered study. Changes in IL11 expression may be a link to the intestinal inflammation frequently observed in patients with HSCR.
Keywords
interleukin 6 signal transducerCLLgp130CD11cGORALDH2Sema3Nup98NRG1TIAIL11GDNFHSCRHWREGFIL6STSCDAPCMAFHO1Janus kinaseMAPKSTATantigen-presenting cellAngiotensinogenRehInterleukin 11Sickle cell diseaseChronic obstructive pulmonary diseaseCOPDHirschsprung's diseaseHirschsprung diseaseHardy-Weinberg equilibriumDinucleotide repeatMicrosatellite repeatsRETdegrees of freedomDinucleotide repeatsWaardenburg syndromeepidermal growth factorconfidence intervalGlial derived neurotrophic factorminor allele frequencyChronic lymphocytic leukemiaSignal transducer and activator of transcriptionGenome-wide association studyGWASMosaicismneuregulin 1AGTheme oxygenase 1mitogen-activated protein kinaseSingle nucleotide polymorphismSNPJAKtotal intestinal aganglionosis
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Authors
Michael G. Haase, Annekatrin Schulze, Sandeep Grover, Ivonne Kemnitz, Inke R. König, Guido Fitze,