Age-dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene.

Idiopathic achalasia is a rare disorder of the oesophagus of unknown aetio-pathogenesis characterized by a myenteric inflammation, aperistalsis and insufficient lower oesophageal sphincter relaxation. Vasoactive intestinal peptide (VIP), present in the myenteric plexus, is involved in smooth muscle relaxation and acts as an anti-inflammatory cytokine. The human VIP receptor 1 gene (VIPR1) is highly polymorphic and may play a role in idiopathic achalasia. One hundred and four consecutive patients and 300 random controls from the same geographic area were typed for five SNPs mapping in the VIPR1 gene. Patients with idiopathic achalasia show a significant difference in allele, genotype and phenotype distribution of SNP rs437876 mapping in intron 4. This association, however, was almost entirely due to the group of patients with late disease onset (P = 0.0005). These results strongly suggest that idiopathic achalasia is a heterogeneous disease with a different aetiology in cases with early or late disease onset.

Effects of intraluminal acidification on oesophageal motor activity.

This study assessed the effect of prolonged intraluminal acidification on the motor activity of the entire oesophageal body (under controlled conditions). Intraoesophageal pressures were recorded in 13 endoscopy negative subjects with gastro-oesophageal reflux disease in whom saline, HC1 0.1 N, and saline solutions were infused (1.5 ml/min) blindly in the oesophageal body, 6 cm distal to the upper oesophageal sphincter for three consecutive periods of 45 minutes each. These findings were compared with those of a control group. Intraoesophageal acidification caused an increase in the deglutition frequency (p < 0.02), the occurrence of multipeaked waves (p < 0.04) as well as a decrease of the propagating velocity (p < 0.04) of the primary peristaltic contractions. Furthermore, intraoesophageal acidification determined an increase, at all levels of the oesophagus, of the duration (p < 0.04) and, more noticeable in the proximal oesophageal body, of the amplitude (p < 0.02) of primary peristaltic contraction waves. In conclusion prolonged intraoesophageal acidification can considerably affect frequency of deglutition, morphology, and propagating patterns of primary peristaltic contractions. This study shows that these effects are independent from volume distension of the oesophagus and supports the presence of acid sensitive receptors in the oesophageal mucosa.