Application of HapMap data to the evaluation of 8 candidate genes for pediatric slow transit constipation Merce ` Garcia-Barcelo a,b,1 , Sebastian K. King c,d,e,1 , Xiaoping Miao a,1 , Man-ting So a,b , William T. Holden f , Jason H. Moore f , Jonathan R. Sutcliffe c , John M. Hutson c,d,e , Paul K.H. Tam a,b, * a Division of Paediatric Surgery, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China b Genome Research Centre, The University of Hong Kong, Hong Kong SAR, China c Department of General Surgery, Royal Children’s Hospital, Melbourne, Australia d Department of Paediatrics, University of Melbourne, Australia e F. Douglas Stephens Surgical Research Laboratory, Murdoch Childrens Research Institute, Melbourne, Australia f Computational Genetics Laboratory, Department of Genetics, Dartmouth Medical School, Lebanon, NH 03756, USA 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. D 2007 Elsevier Inc. All rights reserved. Chronic constipation affects 3% of all children and is the principal reason for 25% of pediatric gastroenterology consults [1-5]. The symptoms of chronic constipation are known to significantly increase childhood morbidity. Recent recognition of slow colonic transit as a cause for chronic constipation in children [6] has led to detailed investigations into the patterns of colonic transit slowing [7], as well as the abnormalities underlying the various dysmotilities. Pediatric slow transit constipation (STC) is characterized by a reduction in stooling frequency to less than 3 episodes 0022-3468/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2006.12.014 * Corresponding author. Division of Paediatric Surgery, Department of Surgery, University of Hong Kong Medical Centre; Queen Mary Hospital, Hong Kong SAR, P.R. China. Tel.: +852 2855 4850; fax: +852 2817 3155. E-mail address: paultam@hkucc.hku.hk (P.K.H. Tam). 1 These authors contributed equally to this study. Index words: Candidate genes; Neurotransmitters; Pediatric slow transit constipation Journal of Pediatric Surgery (2007) 42, 666 – 671 www.elsevier.com/locate/jpedsurg