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European Journal of Human Genetics

Publication date: 2016-08-01
Volume: 24 Pages: 1228 - 1231
Publisher: Nature Publishing Group

Author:

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 ; Schwämmle, 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 Ha ; Wijmenga, Cisca ; Lang, Hauke ; Czene, Kamila ; Hall, Per ; de Bakker, Paul Iw ; Vieth, Michael ; Nöthen, Markus M ; Schulz, Henning G ; Adrych, Krystian ; Gąsiorowska, Anita ; Paradowski, Leszek ; Wallner, Grzegorz ; Boeckxstaens, Guy ; Gockel, Ines ; Hartleb, Marek ; Kostic, Srdjan ; Dziurkowska-Marek, Anna ; Lindblad, Mats ; Nilsson, Magnus ; Knapp, Michael ; Thorell, Anders ; Marek, Tomasz ; Dąbrowski, Andrzej ; Małecka-Panas, Ewa ; Schumacher, Johannes

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Genetics & Heredity, Esophageal Achalasia, Europe, Female, HLA-DQ beta-Chains, Humans, Male, Mutagenesis, Insertional, Mutation Rate, Polymorphism, Genetic, Prevalence, White People, 0604 Genetics, 1103 Clinical Sciences, 3105 Genetics, 3202 Clinical sciences

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 Pcombined=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.European Journal of Human Genetics advance online publication, 6 January 2016; doi:10.1038/ejhg.2015.262.