6533b861fe1ef96bd12c448d

RESEARCH PRODUCT

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

Justyna Wasielica-bergerGiovanni SarnelliAntonio Ruiz De LeónMichael ViethAnders ThorellMagdalena Gawron-kiszkaMichaela MüllerAndrzej DąbrowskiPer HallJonna BisterV. AnneseMarkus M. NöthenBurkhard H.a. Von RahdenMagnus NilssonGuy E. BoeckxstaensAnna MokrowieckaCisca WijmengaJulio Perez De La SernaLeszek ParadowskiMarek L. KowalskiHenning G. SchulzUberto FumagalliTomasz MarekMarek MajewskiStephan L. HaasJohannes SchumacherAgata MulakSrdjan KosticRiccardo RosatiGrzegorz WallnerTill SchwämmleLothar VeitsMarek HartlebZeeshan AteebMichael KnappJessica BeckerAnna LatianoPaul I.w. De BakkerInes GockelStefan NiebischElena UrcelayKrystian AdrychMats LindbladFrank LenzeHauke LangAnita GąsiorowskaEwa Małecka-panasLuigi LaghiMira M. WoutersTimo HessMaria JaniakAnna Dziurkowska-marekPeter ElbeRosario CuomoJose Luis SantiagoKamila Czene

subject

0301 basic medicineMaleEuropean Continental Ancestry GroupShort ReportAchalasiaHuman leukocyte antigenWhite People03 medical and health sciences0302 clinical medicineSwedish populationGeneticGenetics esophageal achalasiaMutation RateGeneticsmedicineotorhinolaryngologic diseasesPrevalenceHLA-DQ beta-ChainsHumansIn patientEsophagusRisk factorGenetics (clinical)GeneticsHLA-DQ beta-ChainPolymorphism Geneticbusiness.industryEuropean populationmedicine.diseaseEsophageal AchalasiaEuropeMutagenesis Insertional030104 developmental biologymedicine.anatomical_structureAttributable risk030211 gastroenterology & hepatologyFemalebusinessHumanDemography

description

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.European Journal of Human Genetics advance online publication, 6 January 2016; doi:10.1038/ejhg.2015.262. ispartof: European Journal of Human Genetics vol:24 issue:8 pages:1228-1231 ispartof: location:England status: published

yearjournalcountryeditionlanguage
2016-08-01
https://hdl.handle.net/20.500.12530/27981