title: Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population.
abstract: BACKGROUND
  Infantile hypertrophic pyloric stenosis (IHPS) is one of the most common gastrointestinal obstructions in the infancy requiring surgery. Reduced expression of neuronal nitric oxide synthase (nNOS), which plays an important role in the regulation of the human pyloric muscle, is thought to underlie IHPS. The role of nNOS in IHPS has been supported by the genetic association of a functional regulatory nNOS polymorphism (-84G>A) with IHPS in whites. We reasoned that the corroboration of this association in a population of different ethnic origin would prompt follow-up studies and further investigation of the IHPS pathology at molecular level. Thus, we attempted to reproduce the original findings in a Chinese population of comparable size in what would be the first genetic study on IHPS conducted in Chinese.
  
  
  METHODS
  nNOS -84G>A genotypes were analyzed in 56 patients and 86 controls by polymerase chain reaction and DNA sequencing. Logistic regression was used to compute odds ratios.
  
  
  RESULTS
  Our study could not corroborate the association previously reported. Although the frequency of the IHPS-associated allele (-84A) in controls (0.205) was similar to that reported for white controls, there was a dramatic difference in -84A frequencies between white and Chinese patients (0.198). Similarly, there was no difference in the nNOS -84G>A genotype distribution between patients and controls, even when the GA and AA genotypes were combined to compare GG genotype (odds ratio, 1.01; 95% confidence interval, 0.47-2.19).
  
  
  CONCLUSIONS
  Failure to replicate the initial finding does not detract from its validity, because genetic effects may differ across populations. Differences across populations in linkage disequilibrium and/or allele frequencies may contribute to this lack of replication. The role nNOS in IHPS awaits further investigation.
authors.affiliation: Department of Surgery, Shenzhen Children's Hospital, Shenzhen, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Maria-Mercè
authors.initials: MM
authors.lastname: Garcia-Barceló
authors.forename: Man-ting
authors.initials: MT
authors.lastname: So
authors.forename: Wai-kiu
authors.initials: WK
authors.lastname: Tang
authors.forename: Xiao
authors.initials: X
authors.lastname: Dong
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Mao
authors.forename: Elly Sau-wai
authors.initials: ES
authors.lastname: Ngan
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Vincent Chi-hang
authors.initials: VC
authors.lastname: Lui
authors.forename: Kenneth Kak-yuen
authors.initials: KK
authors.lastname: Wong
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Paul Kwong-hang
authors.initials: PK
authors.lastname: Tam
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D011110:Polymorphism, Genetic; D046248:Pyloric Stenosis, Hypertrophic / Q000235:genetics*
chemical_list: D052248:Nitric Oxide Synthase Type I