Presence of a protective allele for achalasia on the central region of themajor histocompatibility complex

Idiopathic achalasia is a motility disorder of the esophagus whose etiology is unknown. An association between HLA genes and susceptibility to achalas ia which suggests a possible immunogenetic mechanism has been reported rece ntly. This study was designed to examine the HLA class II association in a large group of achalasia patients further and to investigate the distributi on of TNFa and TNFb microsatellites in these patients. The study population , all Spanish, white and unrelated, consisted of 115 consecutive patients a nd 339 healthy controls. All of the patients had been diagnosed with primar y achalasia of the esophagus with manometric, radiographic and endoscopic s tudies. All studies were performed on DNA samples after locus-specific ampl ification with the polymerase chain reaction: HLA-DRB1, DQA1 and DQB1 were typed by dot-blot hybridization and the size of the TNFa and TNFb microsate llites was measured using a semi automatic method. The broad allele HLA-DQ1 was seen to be weakly associated with achalasia. The TNFall allele and the DRB1*1501-DQA1*0102-DQB1*0602 haplotype were reduced in achalasia patients but the stratified analyses showed that this was true only when both were present in the same individual. These results confirm the association betwe en achalasia and HLA-DQ1 allele and suggest that TNFall is a marker for a p rotective allele for the disease, present on the B7-DRB1*1501 (7.1) ancestr al haplotype in our population.