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

Abstract

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.

Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study

“…In addition, when the association analysis was undertaken considering age as discriminating factor, our study showed no association between age of onset of the disease and NOSs gene polymorphisms. However, in the study by Paladini et al, 47 only late onset achalasia was associated with VIPR1 gene polymorphisms (rs437876 and rs896). A large sample size of patients and control was the strength of the study.…”

Achalasia: will genetic studies provide insights?

“…1). Interestingly, one study has reported an association between a VIPR1 polymorphism that promotes the proinflammatory response and late onset, but not early onset, forms of achalasia ([50 years) (Paladini et al 2009). This finding may suggest that early-and late-onset forms of idiopathic achalasia are genetically distinct disorders (Sarnelli 2009) although this finding requires replication (Fig.…”

Association of IL10 promoter polymorphisms with idiopathic achalasia

“…The role of polymorphisms in the ALADIN gene, involved in the triple-A syndrome (characterized by achalasia, alacrima, and adrenal abnormalities), and NOS gene polymorphisms was studied with negative results [11][12][13]. A functional polymorphism in the lymphoid tyrosine phosphatase N22 gene (PTPN22) has been described as a susceptibility factor for women with achalasia [14] and Paladini et al demonstrated an association between achalasia and the human vasoactive intestinal peptide receptor 1 gene (VIPR1) in patients with late disease onset [15]. In a recent study, we described that the Arg381Gln IL23R variant confers predisposition to achalasia [16].…”