Background/aims: Achalasia is known to result from degeneration of inhibitory neurons, which are mostly nitrinergic. Characteristic features of achalasia include incomplete lower esophageal sphincter (LES) relaxation and esophageal aperistalsis. Nitric oxide (NO), pro-duced by NO synthase (NOS), plays an important role in peristalsis and LES relaxation. Therefore, we evaluated genetic poly-morphisms of NOS gene isoforms (endothelial NOS [eNOS], inducible NOS [iNOS], and neuronal NOS [nNOS]) in patients with achalasia and healthy subjects (HS).
Methods: Consecutive patients with achalasia (diagnosed using esophageal manometry) and HS were genotyped for 27-base pair (bp) eNOS variable number of tandem repeats (VNTR), iNOS22G/A (rs1060826), nNOS C/T (rs2682826) polymorphisms by polymer-ase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively.
Results: Among 183 patients (118 [64.5%] male, age 39.5 ± 13.0 years) with achalasia and 366 HS (254 [69.4%] male, age 40.8 ± 11.0 years), eNOS4a4a genotype of 27-bp VNTR was more common among achalasia than HS (20 [10.9%] vs 13 [3.6%]; P < 0.001; OR, 3.72; 95% CI, 1.8-7.7). Patients with achalasia had iNOS22GA genotypes more often than HS (95 [51.9%] vs 93 [25.4%]; P < 0.001; OR, 3.0; 95% CI, 2.1-4.4). Frequency of genotypes GA + AA was higher in patients than HS (97 [53%] vs 107 [29.2%]; P < 0.001; OR, 2.7; 95% CI, 1.8-3.9). Also, nNOS29TT variant genotype in rs2682826 was more com-mon among patients compared to HS (14 [7.7%] vs 6 [1.6%]; P < 0.001; OR, 5.91; 95% CI, 2.2-15.8).
Conclusions: Achalasia is associated with eNOS4a4a, iNOS22GA, and nNOS29TT genotypes. This may suggest that polymorphisms of eNOS, iNOS, and nNOS genes are risk factors for achalasia.
Keywords: Esophageal motility disorder; Genes; Motor dysphagia; Nitric oxide; Polymorphism.