An original Eurasian haplotype, HLA-DRB1*14:54-DQB1*05:03, influences the susceptibility to idiopathic achalasia

<div><p>Idiopathic achalasia is a relatively infrequent esophageal motor disorder for which major histocompatibility complex (MHC) genes are well-identified risk factors. However, no information about HLA-achalasia susceptibility in Mexicans has previously been reported. We studied a group of 91 patients diagnosed with achalasia and 234 healthy controls with Mexican admixed ancestry. HLA alleles and conserved extended haplotypes were analyzed using high-resolution HLA typing based on Sanger and next-generation sequencing technologies. Admixture estimates were determined using HLA-B and short tandem repeats. Results were analyzed by non-parametric statistical analysis and Bonferroni correction. P-values < 0.05 were considered significant. Patients with achalasia had 56.7% Native American genes, 24.7% European genes, 16.5% African genes and 2.0% Asian genes, which was comparable with the estimates in the controls. Significant increases in the frequencies of alleles DRB1*14:54 and DQB1*05:03 and the extended haplotypes DRB1*14:54-DQB1*05:03 and DRB1*11:01-DQB1*03:01, even after Bonferroni correction (<i>p</i>C<0.05), were found in the achalasia group compared to those in the controls. Concluding, the HLA class II alleles HLA-DRB1*14:54:01 and DQB1*05:03:01 and the extended haplotype are risk factors for achalasia in mixed-ancestry Mexican individuals. These results also suggest that the HLA-DRB1*14:54-DQB1*05:03 haplotype was introduced by admixture with European and/or Asian populations.</p></div

HLA-B/-C/-DRB1/-DQB1 conserved extended haplotypes in achalasia patients and healthy controls.

<p>HLA-B/-C/-DRB1/-DQB1 conserved extended haplotypes in achalasia patients and healthy controls.</p

Gene frequencies of HLA-DQB1 in achalasia patients and healthy controls.

<p>Gene frequencies of HLA-DQB1 in achalasia patients and healthy controls.</p

Gene frequencies of HLA-DRB1 in achalasia patients and healthy controls.

<p>Gene frequencies of HLA-DRB1 in achalasia patients and healthy controls.</p

Most frequent HLA-A/-B/-C/-DRB1/-DQB1 conserved extended haplotypes in Achalasia patients and healthy controls.

<p>Most frequent HLA-A/-B/-C/-DRB1/-DQB1 conserved extended haplotypes in Achalasia patients and healthy controls.</p

Estimations of genetic diversity of HLA class I and class II loci in Mexican admixed individuals with achalasia and controls.

<p>Estimations of genetic diversity of HLA class I and class II loci in Mexican admixed individuals with achalasia and controls.</p

Frequencies of HLA-DRB1/-DQB1 block in achalasia patients and healthy controls.

<p>Frequencies of HLA-DRB1/-DQB1 block in achalasia patients and healthy controls.</p