Application of HapMap data to the evaluation of 8 candidate genes for pediatric slow transit constipation

J Pediatr Surg. 2007 Apr;42(4):666-71. doi: 10.1016/j.jpedsurg.2006.12.014.

Abstract

Background: Slow transit constipation (STC) affects up to 3% of all children and is an increasingly recognized cause of chronic constipation in children. We conducted a pilot study to investigate whether genes encoding neurotransmitters (TAC1, TAC3, VIP, NOS1) and receptors (TACR1, TACR2, TACR3, KIT) could be responsible for STC.

Methods: One hundred seventeen tag single nucleotide polymorphisms (SNPs), distributed among the candidate genes, were selected from HapMap data and genotyped using Sequenom (San Diego, CA) technology in 35 affected families. Evaluation of association was performed by transmission disequilibrium test and multilocus analysis.

Results: Five SNPs (rs3771863, rs4580655, rs11722288, rs4563545, and rs3782221) in the TACR1, TACR3, KIT, and NOS1 genes were found to be potentially associated with STC, although the significance of these results does not withstand correction for multiple testing.

Conclusions: Our data indicate that 5 SNPs in the NOS1, TACR1, TACR3, and KIT genes could be involved in STC, especially rs3771863 in intron 1 of TACR1, which showed the highest association.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chronic Disease
  • Constipation / genetics*
  • Constipation / physiopathology
  • Enteric Nervous System / metabolism*
  • Female
  • Gastrointestinal Transit
  • Genotype*
  • Humans
  • Linkage Disequilibrium
  • Male
  • Neurotransmitter Agents / genetics*
  • Neurotransmitter Agents / metabolism
  • Nitric Oxide Synthase Type I / genetics
  • Nitric Oxide Synthase Type I / metabolism
  • Polymorphism, Single Nucleotide*
  • Receptors, Neurotransmitter / genetics
  • Receptors, Neurotransmitter / metabolism
  • Vasoactive Intestinal Peptide / genetics
  • Vasoactive Intestinal Peptide / metabolism

Substances

  • Neurotransmitter Agents
  • Receptors, Neurotransmitter
  • Vasoactive Intestinal Peptide
  • Nitric Oxide Synthase Type I