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Genome-wide linkage analysis in families with infantile hypertrophic pyloric stenosis indicates novel susceptibility loci

Svenningsson, Anna; Soderhall, Cilla; Persson, Sofia; Lundberg, Fredrik; Luthman, Holger LU ; Chung, Eddie; Gardiner, Mark; Kockum, Ingrid and Nordenskjold, Agneta (2012) In Journal of Human Genetics 57(2). p.115-121
Abstract
Infantile hypertrophic pyloric stenosis (IHPS) is a common cause of upper gastrointestinal obstruction during infancy. A multifactorial background of the disease is well established. Multiple susceptibility loci including the neuronal nitric oxide synthase (NOS1) gene have previously been linked to IHPS, but contradictory results of linkage studies in different materials indicate genetic heterogeneity. To identify IHPS susceptibility loci, we conducted a genome-wide linkage analysis in 37 Swedish families. In regions where the Swedish material showed most evidence in favor of linkage, 31 additional British IHPS families were analyzed. Evidence in favor of significant linkage was observed in the Swedish material to two loci on chromosome... (More)
Infantile hypertrophic pyloric stenosis (IHPS) is a common cause of upper gastrointestinal obstruction during infancy. A multifactorial background of the disease is well established. Multiple susceptibility loci including the neuronal nitric oxide synthase (NOS1) gene have previously been linked to IHPS, but contradictory results of linkage studies in different materials indicate genetic heterogeneity. To identify IHPS susceptibility loci, we conducted a genome-wide linkage analysis in 37 Swedish families. In regions where the Swedish material showed most evidence in favor of linkage, 31 additional British IHPS families were analyzed. Evidence in favor of significant linkage was observed in the Swedish material to two loci on chromosome 2q24 (non-parametric linkage (NPL)=3.77) and 7p21 (NPL=4.55). In addition, evidence of suggestive linkage was found to two loci on chromosome 6p21 (NPL=2.97) and 12q24 (NPL=2.63). Extending the material with British samples did not enhance the level of significance. Regions with linkage harbor interesting candidate genes, such as glucagon-like peptide-2 (GLP-2 encoded by the glucagon gene GCG), NOS1, motilin (MLN) and neuropeptide Y (NPY). The coding exons for GLP-2, and NPY were screened for mutations with negative results. In conclusion, we could confirm suggestive linkage to the region harboring the NOS1 gene and detected additional novel susceptibility loci for IHPS. Journal of Human Genetics (2012) 57, 115-121; doi:10.1038/jhg.2011.137; published online 8 December 2011 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
families, infantile hypertrophic pyloric stenosis, linkage
in
Journal of Human Genetics
volume
57
issue
2
pages
115 - 121
publisher
Springer
external identifiers
  • wos:000300826000007
  • scopus:84857708611
ISSN
1434-5161
DOI
10.1038/jhg.2011.137
language
English
LU publication?
yes
id
b1cbb83c-55ca-4ce4-91ac-45e24b88b0ec (old id 2384463)
date added to LUP
2012-04-02 09:23:44
date last changed
2017-01-01 04:11:07
@article{b1cbb83c-55ca-4ce4-91ac-45e24b88b0ec,
  abstract     = {Infantile hypertrophic pyloric stenosis (IHPS) is a common cause of upper gastrointestinal obstruction during infancy. A multifactorial background of the disease is well established. Multiple susceptibility loci including the neuronal nitric oxide synthase (NOS1) gene have previously been linked to IHPS, but contradictory results of linkage studies in different materials indicate genetic heterogeneity. To identify IHPS susceptibility loci, we conducted a genome-wide linkage analysis in 37 Swedish families. In regions where the Swedish material showed most evidence in favor of linkage, 31 additional British IHPS families were analyzed. Evidence in favor of significant linkage was observed in the Swedish material to two loci on chromosome 2q24 (non-parametric linkage (NPL)=3.77) and 7p21 (NPL=4.55). In addition, evidence of suggestive linkage was found to two loci on chromosome 6p21 (NPL=2.97) and 12q24 (NPL=2.63). Extending the material with British samples did not enhance the level of significance. Regions with linkage harbor interesting candidate genes, such as glucagon-like peptide-2 (GLP-2 encoded by the glucagon gene GCG), NOS1, motilin (MLN) and neuropeptide Y (NPY). The coding exons for GLP-2, and NPY were screened for mutations with negative results. In conclusion, we could confirm suggestive linkage to the region harboring the NOS1 gene and detected additional novel susceptibility loci for IHPS. Journal of Human Genetics (2012) 57, 115-121; doi:10.1038/jhg.2011.137; published online 8 December 2011},
  author       = {Svenningsson, Anna and Soderhall, Cilla and Persson, Sofia and Lundberg, Fredrik and Luthman, Holger and Chung, Eddie and Gardiner, Mark and Kockum, Ingrid and Nordenskjold, Agneta},
  issn         = {1434-5161},
  keyword      = {families,infantile hypertrophic pyloric stenosis,linkage},
  language     = {eng},
  number       = {2},
  pages        = {115--121},
  publisher    = {Springer},
  series       = {Journal of Human Genetics},
  title        = {Genome-wide linkage analysis in families with infantile hypertrophic pyloric stenosis indicates novel susceptibility loci},
  url          = {http://dx.doi.org/10.1038/jhg.2011.137},
  volume       = {57},
  year         = {2012},
}