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First genotype-phenotype study reveals HLA-DQ?1 insertion heterogeneity in high-resolution manometry achalasia subtypes.

ABSTRACT: Background:Achalasia is a primary oesophageal motility disorder. Although aetiology remains mainly unknown, a genetic risk variant, rs28688207 in HLA-DQB1, showed strong achalasia association suggesting involvement of immune-mediated processes in the pathogenesis. High-resolution manometry recognises three types of achalasia. The aim of our study was to perform the first genotype-phenotype analysis investigating the frequency of rs28688207 across the high-resolution manometry subtypes. Methods:This was a cross-sectional retrospective study. Achalasia patients from tertiary centres in the Czech Republic (n?=?163), Germany (n?=?114), Greece (n?=?70) and controls were enrolled. All subjects were genotyped for the rs28688207 insertion. The Kruskal-Wallis test was used for the genotype-phenotype analysis. Results:A total of 347 achalasia patients (type I - 89, II - 210, III - 48) were included. The overall frequency of the rs28688207 was 10.3%. The distribution of the insertion was significantly different across the high-resolution manometry subtypes (p?=?0.038), being most prevalent in type I (14.6%), followed by type II (9.5%) and III (6.3%). Conclusion:The frequency of the HLA-DQB1 insertion differs among high-resolution manometry achalasia subtypes. The insertion is most prevalent in type I, suggesting that immune-mediated mechanisms triggered by the insertion may play a more prominent role in the pathogenesis of this subtype.

SUBMITTER: Vackova Z

PROVIDER: S-EPMC6374847 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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First genotype-phenotype study reveals HLA-DQβ1 insertion heterogeneity in high-resolution manometry achalasia subtypes.

Vackova Zuzana Z Niebisch Stefan S Triantafyllou Tania T Becker Jessica J Hess Timo T Kreuser Nicole N Kanoni Stavroula S Deloukas Panos P Schüller Vitalia V Heinrichs Sophie Km SK Thieme René R Nöthen Markus M MM Knapp Michael M Spicak Julius J Gockel Ines I Schumacher Johannes J Theodorou Dimitris D Martinek Jan J

United European gastroenterology journal 20181003 1

<h4>Background</h4>Achalasia is a primary oesophageal motility disorder. Although aetiology remains mainly unknown, a genetic risk variant, rs28688207 in HLA-DQB1, showed strong achalasia association suggesting involvement of immune-mediated processes in the pathogenesis. High-resolution manometry recognises three types of achalasia. The aim of our study was to perform the first genotype-phenotype analysis investigating the frequency of rs28688207 across the high-resolution manometry subtypes.<h ...[more]

PMID: 30788115

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Project description:BACKGROUND & AIMS:Esophageal retention is typically evaluated by timed-barium esophagram in patients treated for achalasia. Esophageal bolus clearance can also be evaluated using high-resolution impedance manometry. We evaluated the associations of conventional and novel high-resolution impedance manometry metrics, esophagram, and patient-reported outcomes (PROs) in achalasia. METHODS:We performed a prospective study of 70 patients with achalasia (age, 20-81 y; 30 women) treated by pneumatic dilation or myotomy who underwent follow-up evaluations from April 2013 through December 2015 (median, 12 mo after treatment; range, 3-183 mo). Patients were assessed using timed-barium esophagrams, high-resolution impedance manometry, and PROs, determined from Eckardt scores (the primary outcome) and the brief esophageal dysphagia questionnaire. Barium column height was measured from esophagrams taken 5 minutes after ingestion of barium (200 mL). Impedance-manometry was analyzed for bolus transit (dichotomized) and with a customized MATLAB program (The MathWorks, Inc, Natick, MA) to calculate the esophageal impedance integral (EII) ratio. RESULTS:Optimal cut points to identify a good PRO (defined as Eckardt score of ?3) were esophagram barium column height of 3 cm (identified patients with a good PRO with 63% sensitivity and 75% specificity) and an EII ratio of 0.41 (identified patients with a good PRO with 83% sensitivity and 75% specificity). Complete bolus transit identified patients with a good PRO with 28% sensitivity and 75% specificity. Of the 25 patients who met these cut points for both esophagram barium column height and EII ratio, 23 (92%) had a good PRO. Of the 17 patients who met neither cut point, 14 (82%) had a poor PRO (Eckardt score above 3). CONCLUSIONS:In a prospective study of 70 patients with achalasia, we found EII ratio identified patients with good PROs with higher levels of sensitivity (same specificity) than timed-barium esophagram or impedance-manometry bolus transit assessments. The EII ratio should be added to achalasia outcome evaluations that involve high-resolution impedance manometry as an independent measure and to complement timed-barium esophagram.

Dataset Information

First genotype-phenotype study reveals HLA-DQ?1 insertion heterogeneity in high-resolution manometry achalasia subtypes.

Publications

First genotype-phenotype study reveals HLA-DQβ1 insertion heterogeneity in high-resolution manometry achalasia subtypes.

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