BACKGROUND & AIMS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: Idiopathic achalasia is associated with HLA alleles in a 
race-specific manner. These results support an immunogenetic mechanism in the 
pathogenesis of idiopathic achalasia.