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Your search keyword '"de la Serna JP"' showing total 2 results
Start Over Author "de la Serna JP" Topic hla-dq beta-chains
2 results on '"de la Serna JP"'

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

Author

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, Schwämmle 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 BH, Wijmenga C, Lang H, Czene K, Hall P, de Bakker PI, Vieth M, Nöthen MM, Schulz HG, Adrych K, Gąsiorowska 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, Dąbrowski A, Małecka-Panas E, and Schumacher J

Subjects
Esophageal Achalasia epidemiology, Esophageal Achalasia ethnology, Europe, Female, Humans, Male, Mutation Rate, Polymorphism, Genetic, Prevalence, White People genetics, Esophageal Achalasia genetics, HLA-DQ beta-Chains genetics, Mutagenesis, Insertional
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.

Published
2016
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2. Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia.

Author

Gockel I, Becker J, Wouters MM, Niebisch S, Gockel HR, Hess T, Ramonet D, Zimmermann J, Vigo AG, Trynka G, de León AR, de la Serna JP, Urcelay E, Kumar V, Franke L, Westra HJ, Drescher D, Kneist W, Marquardt JU, Galle PR, Mattheisen M, Annese V, Latiano A, Fumagalli U, Laghi L, Cuomo R, Sarnelli G, Müller M, Eckardt AJ, Tack J, Hoffmann P, Herms S, Mangold E, Heilmann S, Kiesslich R, von Rahden BH, Allescher HD, Schulz HG, Wijmenga C, Heneka MT, Lang H, Hopfner KP, Nöthen MM, Boeckxstaens GE, de Bakker PI, Knapp M, and Schumacher J

Subjects
Alleles, Amino Acid Substitution, Case-Control Studies, Esophageal Achalasia immunology, Female, Genetic Association Studies methods, Genetic Predisposition to Disease, HLA-DQ Antigens chemistry, Haplotypes, Humans, Logistic Models, Male, Models, Molecular, Polymorphism, Single Nucleotide, Esophageal Achalasia genetics, HLA-DQ Antigens genetics, HLA-DQ alpha-Chains genetics, HLA-DQ beta-Chains genetics
Abstract

Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQβ1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P=1.73×10(-19)). In addition, two amino acid substitutions in the extracellular domain of HLA-DQα1 at position 41 (lysine encoded by HLA-DQA1*01:03; P=5.60×10(-10)) and of HLA-DQβ1 at position 45 (glutamic acid encoded by HLA-DQB1*03:01 and HLA-DQB1*03:04; P=1.20×10(-9)) independently confer achalasia risk. Our study implies that immune-mediated processes are involved in the pathophysiology of achalasia.

Published
2014
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