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.
The HLA-DQβ1 insertion is a strong Achalasia risk factor and displays a geospatial north-south gradient among Europeans (2016) , 24 (8), pp. 1228-1231 / 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. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - 24:8(2016), pp. 1228-1231. [doi: 10.1038/ejhg.2015.262]
The HLA-DQβ1 insertion is a strong Achalasia risk factor and displays a geospatial north-south gradient among Europeans (2016) , 24 (8), pp. 1228-1231.
Laghi L;
2016-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
