The HLA-DQβ1 insertion is a strong Achalasia risk factor and displays a geospatial north-south gradient among Europeans

Jessica Becker, Stephan L. Haas, Anna Mokrowiecka, Justyna Wasielica-Berger, Zeeshan Ateeb, Jonna Bister, Peter Elbe, Marek Kowalski, Magdalena Gawron-Kiszka, Marek Majewski, Agata Mulak, Maria Janiak, Mira M. Wouters, Till Schw'mmle, Timo Hess, Lothar Veits, Stefan Niebisch, José L. Santiago, Antonio Ruiz De León, Julio Pérez De la SernaElena Urcelay, Vito Annese, Anna Latiano, Uberto Fumagalli, Riccardo Rosati, Luigi Laghi, Rosario Cuomo, Frank Lenze, Giovanni Sarnelli, Michaela Müller, Burkhard H.A. Von Rahden, Cisca Wijmenga, Hauke Lang, Kamila Czene, Per Hall, Paul I.W. De Bakker, Michael Vieth, Markus M. Nöthen, Henning G. Schulz, Krystian Adrych, Anita Gasiorowska, Leszek Paradowski, Grzegorz Wallner, Guy E. Boeckxstaens, Ines Gockel, Marek Hartleb, Srdjan Kostic, Anna Dziurkowska-Marek, Mats Lindblad, Magnus Nilsson, Michael Knapp, Anders Thorell, Tomasz Marek, Andrzej Dabrowski, Ewa Małecka-Panas, Johannes Schumacher

Research output: Contribution to journalArticle

Abstract

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10 -04, Sweden P=7.44 × 10 -05). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with P combined =1.67 × 10 -35. In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared with southern Europeans (∼16% in patients and 8% in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.
Original languageEnglish
Pages (from-to)1228 - 1231
Number of pages4
JournalEuropean Journal of Human Genetics
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 1 2016

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Esophageal Achalasia
Poland
Sweden
Italy
Spain
Population
Myenteric Plexus
Lower Esophageal Sphincter
Esophagus
HLA-DQ1 antigen
Neurons
Amino Acids

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Becker, J., Haas, S. L., Mokrowiecka, A., Wasielica-Berger, J., Ateeb, Z., Bister, J., ... Schumacher, J. (2016). The HLA-DQβ1 insertion is a strong Achalasia risk factor and displays a geospatial north-south gradient among Europeans. European Journal of Human Genetics, 24(8), 1228 - 1231. https://doi.org/10.1038/ejhg.2015.262

The HLA-DQβ1 insertion is a strong Achalasia risk factor and displays a geospatial north-south gradient among Europeans. / Becker, Jessica; Haas, Stephan L.; Mokrowiecka, Anna; Wasielica-Berger, Justyna; Ateeb, Zeeshan; Bister, Jonna; Elbe, Peter; Kowalski, Marek; Gawron-Kiszka, Magdalena; Majewski, Marek; Mulak, Agata; Janiak, Maria; Wouters, Mira M.; Schw'mmle, Till; Hess, Timo; Veits, Lothar; Niebisch, Stefan; Santiago, José L.; De León, Antonio Ruiz; De la Serna, Julio Pérez; Urcelay, Elena; Annese, Vito; Latiano, Anna; Fumagalli, Uberto; Rosati, Riccardo; Laghi, Luigi; Cuomo, Rosario; Lenze, Frank; Sarnelli, Giovanni; Müller, Michaela; Von Rahden, Burkhard H.A.; Wijmenga, Cisca; Lang, Hauke; Czene, Kamila; Hall, Per; De Bakker, Paul I.W.; Vieth, Michael; Nöthen, Markus M.; Schulz, Henning G.; Adrych, Krystian; Gasiorowska, Anita; Paradowski, Leszek; Wallner, Grzegorz; Boeckxstaens, Guy E.; Gockel, Ines; Hartleb, Marek; Kostic, Srdjan; Dziurkowska-Marek, Anna; Lindblad, Mats; Nilsson, Magnus; Knapp, Michael; Thorell, Anders; Marek, Tomasz; Dabrowski, Andrzej; Małecka-Panas, Ewa; Schumacher, Johannes.

In: European Journal of Human Genetics, Vol. 24, No. 8, 01.08.2016, p. 1228 - 1231.

Research output: Contribution to journalArticle

Becker, J, Haas, SL, Mokrowiecka, A, Wasielica-Berger, J, Ateeb, Z, Bister, J, Elbe, P, Kowalski, M, Gawron-Kiszka, M, Majewski, M, Mulak, A, Janiak, M, Wouters, MM, Schw'mmle, T, Hess, T, Veits, L, Niebisch, S, Santiago, JL, De León, AR, De la Serna, JP, Urcelay, E, Annese, V, Latiano, A, Fumagalli, U, Rosati, R, Laghi, L, Cuomo, R, Lenze, F, Sarnelli, G, Müller, M, Von Rahden, BHA, Wijmenga, C, Lang, H, Czene, K, Hall, P, De Bakker, PIW, Vieth, M, Nöthen, MM, Schulz, HG, Adrych, K, Gasiorowska, A, Paradowski, L, Wallner, G, Boeckxstaens, GE, Gockel, I, Hartleb, M, Kostic, S, Dziurkowska-Marek, A, Lindblad, M, Nilsson, M, Knapp, M, Thorell, A, Marek, T, Dabrowski, A, Małecka-Panas, E & Schumacher, J 2016, 'The HLA-DQβ1 insertion is a strong Achalasia risk factor and displays a geospatial north-south gradient among Europeans', European Journal of Human Genetics, vol. 24, no. 8, pp. 1228 - 1231. https://doi.org/10.1038/ejhg.2015.262
Becker, Jessica ; Haas, Stephan L. ; Mokrowiecka, Anna ; Wasielica-Berger, Justyna ; Ateeb, Zeeshan ; Bister, Jonna ; Elbe, Peter ; Kowalski, Marek ; Gawron-Kiszka, Magdalena ; Majewski, Marek ; Mulak, Agata ; Janiak, Maria ; Wouters, Mira M. ; Schw'mmle, Till ; Hess, Timo ; Veits, Lothar ; Niebisch, Stefan ; Santiago, José L. ; De León, Antonio Ruiz ; De la Serna, Julio Pérez ; Urcelay, Elena ; Annese, Vito ; Latiano, Anna ; Fumagalli, Uberto ; Rosati, Riccardo ; Laghi, Luigi ; Cuomo, Rosario ; Lenze, Frank ; Sarnelli, Giovanni ; Müller, Michaela ; Von Rahden, Burkhard H.A. ; Wijmenga, Cisca ; Lang, Hauke ; Czene, Kamila ; Hall, Per ; De Bakker, Paul I.W. ; Vieth, Michael ; Nöthen, Markus M. ; Schulz, Henning G. ; Adrych, Krystian ; Gasiorowska, Anita ; Paradowski, Leszek ; Wallner, Grzegorz ; Boeckxstaens, Guy E. ; Gockel, Ines ; Hartleb, Marek ; Kostic, Srdjan ; Dziurkowska-Marek, Anna ; Lindblad, Mats ; Nilsson, Magnus ; Knapp, Michael ; Thorell, Anders ; Marek, Tomasz ; Dabrowski, Andrzej ; Małecka-Panas, Ewa ; Schumacher, Johannes. / The HLA-DQβ1 insertion is a strong Achalasia risk factor and displays a geospatial north-south gradient among Europeans. In: European Journal of Human Genetics. 2016 ; Vol. 24, No. 8. pp. 1228 - 1231.
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abstract = "Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10 -04, Sweden P=7.44 × 10 -05). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with P combined =1.67 × 10 -35. In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7{\%} in patients and 2{\%} in controls from Sweden and Poland) compared with southern Europeans (∼16{\%} in patients and 8{\%} in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.",
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AU - Becker, Jessica

AU - Haas, Stephan L.

AU - Mokrowiecka, Anna

AU - Wasielica-Berger, Justyna

AU - Ateeb, Zeeshan

AU - Bister, Jonna

AU - Elbe, Peter

AU - Kowalski, Marek

AU - Gawron-Kiszka, Magdalena

AU - Majewski, Marek

AU - Mulak, Agata

AU - Janiak, Maria

AU - Wouters, Mira M.

AU - Schw'mmle, Till

AU - Hess, Timo

AU - Veits, Lothar

AU - Niebisch, Stefan

AU - Santiago, José L.

AU - De León, Antonio Ruiz

AU - De la Serna, Julio Pérez

AU - Urcelay, Elena

AU - Annese, Vito

AU - Latiano, Anna

AU - Fumagalli, Uberto

AU - Rosati, Riccardo

AU - Laghi, Luigi

AU - Cuomo, Rosario

AU - Lenze, Frank

AU - Sarnelli, Giovanni

AU - Müller, Michaela

AU - Von Rahden, Burkhard H.A.

AU - Wijmenga, Cisca

AU - Lang, Hauke

AU - Czene, Kamila

AU - Hall, Per

AU - De Bakker, Paul I.W.

AU - Vieth, Michael

AU - Nöthen, Markus M.

AU - Schulz, Henning G.

AU - Adrych, Krystian

AU - Gasiorowska, Anita

AU - Paradowski, Leszek

AU - Wallner, Grzegorz

AU - Boeckxstaens, Guy E.

AU - Gockel, Ines

AU - Hartleb, Marek

AU - Kostic, Srdjan

AU - Dziurkowska-Marek, Anna

AU - Lindblad, Mats

AU - Nilsson, Magnus

AU - Knapp, Michael

AU - Thorell, Anders

AU - Marek, Tomasz

AU - Dabrowski, Andrzej

AU - Małecka-Panas, Ewa

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