Application of HapMap data to the evaluation of 8 candidate genes for pediatric slow transit constipation.
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.
Garcia-Barcelo
Mercè
M
Division of Paediatric Surgery, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
King
Sebastian K
SK
Miao
Xiaoping
X
So
Man-ting
MT
Holden
William T
WT
Moore
Jason H
JH
Sutcliffe
Jonathan R
JR
Hutson
John M
JM
Tam
Paul K H
PK
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003248:Constipation / Q000235:genetics* / Q000503:physiopathology; D017615:Enteric Nervous System / Q000378:metabolism*; D005260:Female; D005772:Gastrointestinal Transit; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018377:Neurotransmitter Agents / Q000235:genetics* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D014660:Vasoactive Intestinal Peptide; D052248:Nitric Oxide Synthase Type I