title: Association between achalasia and nitric oxide synthase gene polymorphisms.
abstract: BACKGROUND
  Our group previously reported the absence of nitric oxide synthase (NOS) in the gastroesophageal junction of patients with achalasia. NOS exists in three distinct isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible isoform (iNOS). Some studies have shown that NO production is regulated by NOS polymorphisms.
  
  
  OBJECTIVE
  To assess whether some functional polymorphisms in the nNOS, iNOS, or eNOS genes are involved in susceptibility to suffer from achalasia.
  
  
  METHODS
  Genomic DNA from 80 unrelated Spanish Caucasian patients with sporadic achalasia and 144 healthy subjects matched for age (+/-5 yr) and gender was typed by PCR and RFLP methods for the 27-bp variable number of tandem repeat (VNTR) polymorphism in intron 4 of the eNOS gene, a CA microsatellite repeat and a Nla III (C-->T) restriction fragment length polymorphism (RFLP) in exon 29 of the nNOS gene, and two nucleotide substitutions located in exon 16 (C-->T) and exon 22 (G-->A) of the iNOS gene.
  
  
  RESULTS
  No significant differences in carriage, genotype, and allele frequencies of the nNOS, iNOS, or eNOS gene polymorphisms were found between patients with achalasia and controls. Individuals homozygous for genotype iNOS22*A/A tended to be more frequent in achalasia (20%vs 11%, odds ratio [OR] 1.79, 95% confidence interval [CI] 0.89-3.59, p= 0.09) as were those homozygous for the rare eNOS*4a allele (6.2%vs 1.4%, OR 4.5, 95% CI 0.89-22.67, p= 0.1) although the difference did not reach statistical significance. No differences in genotype and allele distribution were found with respect to epidemiological and clinical characteristics of patients with achalasia.
  
  
  CONCLUSIONS
  Our data suggest that NOS gene polymorphisms are not involved in the susceptibility to and nature of the clinical course of sporadic achalasia. However, studies in a greater number of patients are required to analyze the tendency toward a higher prevalence of genotypes iNOS22*A/A and eNOS*4a4a.
authors.affiliation: Institute of Functional and Motor Digestive Disorders, Centro Médico Teknon, Barcelona, Spain.
authors.forename: Fermín
authors.initials: F
authors.lastname: Mearin
authors.forename: María-Asunción
authors.initials: MA
authors.lastname: García-González
authors.forename: Michael
authors.initials: M
authors.lastname: Strunk
authors.forename: Natalia
authors.initials: N
authors.lastname: Zárate
authors.forename: Juán-Ramón
authors.initials: JR
authors.lastname: Malagelada
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
mesh_terms: D000483:Alleles; D004247:DNA / Q000235:genetics*; D004931:Esophageal Achalasia / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D018598:Minisatellite Repeats; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011312:Pressure; D012720:Severity of Illness Index
chemical_list: D004247:DNA; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III