Association of HLA-DR and -DQ alleles with idiopathic achalasia

Idiopathic achalasia is a motility disorder of the esophagus characterized by incomplete relaxation of the lower esophageal sphincter and a loss of normal peristaltic activity in the body of the esophagus. The loss of inhibitory neurons in the distal esophagus, as well as abnormalities in the vagus nerve, dorsal motor nucleus of the vagus nerve, and autonomic nervous system, have been described in achalasia. Although the underlying cause of idiopathic achalasia is unknown, the diffuse neuronal effects found suggest a possible viral or neurodegenerative mechanism. By use of serological methods, a significant association between the HLA-DQ1 phenotype and idiopathic achalasia has been found, suggesting a possible immunogenetic mechanism. To further define immunogenetics in the pathogenesis of idiopathic achalasia, we performed tissue typing in patients with achalasia to determine their specific HLA phenotypes.

We prospectively studied 32 patients (23 white and 9 black) with idiopathic achalasia. Peripheral blood was collected, and HLA-DR and -DQ typing by polymerase chain reaction with sequence-specific primers was performed. Results were compared with those from 268 racially matched local controls.

Idiopathic achalasia and the broad HLA-DQ1 allele were not significantly associated in either population, although a trend was found in white subjects (odds ratio [OR], 2.16; chi2 = 5.36, P corrected [Pc] = 0.0824). Further subtyping in white subjects revealed a significant association between idiopathic achalasia and the DQB1*0602 allele (OR, 3.10; chi2 = 7.32, Pc = 0.0408). A strong trend was also found with the DRB1*15 allele (OR, 2.83; chi2 = 8.11, Pc = 0.0572). In the black population, there was no association between idiopathic achalasia and DQB1*0602 or DRB1*15, but a trend was found with DRB1*12 (OR, 6. 19; chi2 = 5.19, P = 0.0227 uncorrected, Pc = 0.295).

Idiopathic achalasia is associated with HLA alleles in a race-specific manner. These results support an immunogenetic mechanism in the pathogenesis of idiopathic achalasia.