Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population.
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.
Miao
Xiaoping
X
Department of Surgery, Shenzhen Children's Hospital, Shenzhen, China.
Garcia-Barceló
Maria-Mercè
MM
So
Man-ting
MT
Tang
Wai-kiu
WK
Dong
Xiao
X
Wang
Bin
B
Mao
Jianxiong
J
Ngan
Elly Sau-wai
ES
Chen
Yan
Y
Lui
Vincent Chi-hang
VC
Wong
Kenneth Kak-yuen
KK
Liu
Lei
L
Tam
Paul Kwong-hang
PK
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*
D052248:Nitric Oxide Synthase Type I