Dataset Information

The HLA-DQ?1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.

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-DQ?1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQ?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 × 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.

SUBMITTER: Becker J

PROVIDER: S-EPMC4970678 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Becker Jessica J Haas Stephan L SL Mokrowiecka Anna A Wasielica-Berger Justyna J Ateeb Zeeshan Z Bister Jonna J Elbe Peter P Kowalski Marek M Gawron-Kiszka Magdalena M Majewski Marek M Mulak Agata A Janiak Maria M Wouters Mira M MM Schwämmle Till T Hess Timo T Veits Lothar L Niebisch Stefan S Santiago José L JL de León Antonio Ruiz AR de la Serna Julio Pérez JP Urcelay Elena E Annese Vito V Latiano Anna A Fumagalli Uberto U Rosati Riccardo R Laghi Luigi L Cuomo Rosario R Lenze Frank F Sarnelli Giovanni G Müller Michaela M von Rahden Burkhard Ha BH Wijmenga Cisca C Lang Hauke H Czene Kamila K Hall Per P de Bakker Paul Iw PI Vieth Michael M Nöthen Markus M MM Schulz Henning G HG Adrych Krystian K Gąsiorowska Anita A Paradowski Leszek L Wallner Grzegorz G Boeckxstaens Guy E GE Gockel Ines I Hartleb Marek M Kostic Srdjan S Dziurkowska-Marek Anna A Lindblad Mats M Nilsson Magnus M Knapp Michael M Thorell Anders A Marek Tomasz T Dąbrowski Andrzej A Małecka-Panas Ewa E Schumacher Johannes J

European journal of human genetics : EJHG 20160106 8

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 re ...[more]

PMID: 26733285

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Project description:BackgroundThe pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans.MethodsT2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (1H-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model.ResultsA total of 131 individuals were included (54 South Asians [50.1 ± 8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8 ± 7.0 years, 56% men, 48 patients vs. 29 controls)]. The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians [- 0.20 (- 0.36; - 0.03), P = 0.021] and Europeans [- 0.20 (- 0.36; - 0.04), P = 0.017], whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass [+ 22 g (15; 30), P < 0.001] (P for interaction by ethnicity = 0.005) with a lower extracellular volume fraction [- 1.9% (- 3.4; - 0.4), P = 0.013] (P for interaction = 0.114), whilst European T2D patients had a higher myocardial triglyceride content [+ 0.59% (0.35; 0.84), P = 0.001] (P for interaction = 0.002) than their control group.ConclusionsDiabetic cardiomyopathy was characterized by impaired LV diastolic function in South Asians and Europeans. Increased LV mass was solely observed among South Asian T2D patients, whereas differences in myocardial triglyceride content between T2D patients and controls were only present in the European cohort. The diabetic cardiomyopathy phenotype may differ between subsets of T2D patients, for example across ethnicities, and tailored strategies for T2D management may be required.

Dataset Information

The HLA-DQ?1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.

Publications

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

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