Genomic variants in the coding region of neuronal nitric oxide synthase (NOS1) in infantile hypertrophic pyloric stenosis.
BACKGROUND
Infantile hypertrophic pyloric stenosis (IHPS) is a common childhood pathology affecting 1 to 5:1000 newborns, with a genetic background suggested by familial occurrence. Neuronal nitric oxide synthase (NOS1) is a candidate gene owing to its role in the relaxation of smooth musculature and the association of the -84g>a variant of NOS1 with IHPS.


METHODS
We investigated NOS1 through sequencing of the complete NOS1 coding region in DNA from 43 patients with IHPS compared the genotype frequencies to 47 controls using the Cochran-Armitage trend or Fisher exact tests.


RESULTS
We found 19 polymorphisms in the coding region of NOS1. The variants c.3827-42_3827-43 del_insTA and c.+276 c>t were more frequent in IHPS with statistically significant exact P values (P = .010 and P = .039, respectively) yet failed to show significance after Bonferroni adjustment for multiple testing. We have also found a marginally significant occurrence of the variants c.-460A (P = .065) and c.2823+15G (P = .076). There was a significant correlation between the variants c.2706C>T ⬄ c.2823+15A>G, (r(2) = 1.00) and c.3258 C>T ⬄ c.3235+31A>G (r(2) = 1.00).


CONCLUSIONS
We conclude that NOS1 variants are present in patients with IHPS yet show no significant statistical association with the IHPS phenotype, suggesting at best an adjuvant role for NOS1 in IHPS.
Department of Surgery (Pediatric Surgery), Ulm University, D-89075 Ulm, Germany.
Alexandre
A
Serra
Katrin
K
Schuchardt
Jon
J
Genuneit
Clothilde
C
Leriche
Guido
G
Fitze
D020121:5' Untranslated Regions / Q000235:genetics; D004247:DNA / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D046248:Pyloric Stenosis, Hypertrophic / Q000453:epidemiology / Q000235:genetics*
D020121:5' Untranslated Regions; D004247:DNA; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I