The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans
The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans
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DOI：
10.1038/ejhg.2015.262
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发表时间：
2016-08-01
影响因子：
5.2
通讯作者：
Schumacher, Johannes
中科院分区：
文献类型：
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作者：
Becker, Jessica;Haas, Stephan L.;Schumacher, Johannes
特发性贲门失弛缓症是一种严重的食管运动障碍，其特征是由于肌间神经丛中神经元的丧失而导致食管下端括约肌无法松弛。最近，我们在来自中欧、意大利和西班牙的样本集中发现 HLA-DQ beta 1 细胞质尾部的八个氨基酸插入是贲门失弛缓症的强危险因素。在这里，我们测试了 HLA-DQ beta 1 插入是否也会给波兰和瑞典人群带来失弛缓症风险。我们可以重复最初的发现，并且插入显示两个样本中都有很强的贲门失弛缓症相关性（波兰 P= 1.84 x 10(-04)，瑞典 P= 7.44 x 10(-05)）。结合所有五个欧洲数据集 - 中欧、意大利、西班牙、波兰和瑞典 - 插入是与 P-combined= 1.67 x 10(-35) 相关的失弛缓症。此外，我们观察到插入频率显示出地理空间南北梯度。与南欧人相比（来自意大利的患者为 16%，对照组为 8%），这种插入在北欧人中较少见（瑞典和波兰的患者中约为 6-7%，对照组为 2%），并且在南欧人群中表现出更强的归因风险。我们的研究提供的证据表明，贲门失弛缓症的患病率可能因人群而异。
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-DQ beta 1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQ beta 1 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 x 10(-04), Sweden P= 7.44 x 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 x 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 (similar to 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.