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, 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 E, 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
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Eur J Hum Genet. 2016 Aug;24(8):1228-31. doi: 10.1038/ejhg.2015.262. Epub 2016 Jan 6.
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.
特发性贲门失弛缓症是一种严重的食管动力障碍性疾病，其特征是由于肌间神经丛中神经元缺失，导致食管下括约肌无法松弛。最近，我们在一组来自中欧、意大利和西班牙的样本中发现，HLA-DQβ1胞质尾部的一个八氨基酸插入是贲门失弛缓症的强风险因素。在此，我们测试了HLA-DQβ1插入在波兰和瑞典人群中是否也会增加贲门失弛缓症的风险。我们能够重复最初的发现，并且该插入在两个样本中均显示出与贲门失弛缓症的强关联（波兰P = 1.84 × 10(-04)，瑞典P = 7.44 × 10(-05)）。将来自中欧、意大利、西班牙、波兰和瑞典的所有五个欧洲数据集合并后，该插入与贲门失弛缓症的关联为P合并 = 1.67 × 10(-35)。此外，我们观察到该插入的频率呈现出地理空间上的南北梯度。与南欧人相比，该插入在北欧不太常见（瑞典和波兰患者中约为6 - 7%，对照组中约为2%），而在意大利患者中约为16%，对照组中约为8%，并且在南欧人群中显示出更强的归因风险。我们的研究提供了证据表明贲门失弛缓症的患病率在不同人群中可能存在差异。
