title: Genetic variants in RET and risk of Hirschsprung's disease in Southeastern Chinese: a haplotype-based analysis.
abstract: BACKGROUND
  Hirschsprung's disease (HSCR) is a classic oligogenic disorder. Except inactivating mutations of RET, some single nucleotide polymorphisms (SNPs) are identified to be associated with the risk of HSCR. This study was conducted to examine the impact of the haplotypes profile of the reported associated SNPs of RET on the risk of HSCR in a Southeastern Chinese population.
  
  
  METHODS
  Genotypes of -5G > A (rs10900296), -1A > C (rs10900297), c135G > A (rs1800858), c1296A > G (rs1800860), and c2307T > G (rs1800861) were analyzed in 123 HSCR patients and 168 controls by polymerase chain reaction amplification and direct sequencing. Associations with risk of HSCR were estimated by odds ratio (OR) and their 95% confidence intervals (95% CI) using logistic regression.
  
  
  RESULTS
  We observed a significantly increased risk of HSCR associated with the RET -5AA (OR = 17.75, 95% CI = 7.34-42.92), -1CC (OR = 10.89, 95% CI = 3.13-37.85), 135AA (OR = 13.61, 95% CI = 6.14-30.14), 1296GG (OR = 2.40, 95% CI = 1.38-4.18) or 2307GG (OR = 9.79, 95% CI = 4.28-22.43) respectively. The five SNPs were in strong linkage disequilibrium. The haplotype A-C-A-G-G (OR = 5.06, 95% CI = 1.97-12.99) and diplotype A-C-A-G-G/A-C-A-G-G (OR = 21.08, 95% CI = 5.28-84.09) was also associated with the increased risk of HSCR, indicating a cumulative effect of these SNPs on the susceptibility of HSCR.
  
  
  CONCLUSIONS
  These results support the hypothesis that common variations in RET pathway might play an important role in development of HSCR.
authors.affiliation: Department of Pediatric Surgery, Children's Hospital Zhejiang University School of Medicine, Hangzhou, PR China. toujingfa@gmail.com
authors.forename: Jinfa
authors.initials: J
authors.lastname: Tou
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Shengyu
authors.initials: S
authors.lastname: Duan
authors.forename: Weiguang
authors.initials: W
authors.lastname: Liu
authors.forename: Qixing
authors.initials: Q
authors.lastname: Xiong
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Gu
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D016001:Confidence Intervals; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006627:Hirschsprung Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D017720:Molecular Epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012307:Risk Factors
chemical_list: D017931:DNA Primers; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human