title: Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis.
abstract: BACKGROUND
  Pancreatic ductal HCO3(-) secretion is critically dependent on the cystic fibrosis transmembrane conductance regulator chloride channel (CFTR) and the solute-linked carrier 26 member 6 anion transporter (SLC26A6). Deterioration of HCO3(-) secretion is observed in chronic pancreatitis (CP), and CFTR mutations increase CP risk. Therefore, SLC26A6 is a reasonable candidate for a CP susceptibility gene, which has not been investigated in CP patients so far.
  
  
  METHODS
  As a first screening cohort, 106 subjects with CP and 99 control subjects with no pancreatic disease were recruited from the Hungarian National Pancreas Registry. In 60 non-alcoholic CP cases the entire SLC26A6 coding region was sequenced. In the Hungarian cohort variants c.616G > A (p.V206M) and c.1191C > A (p.P397=) were further genotyped by restriction fragment length polymorphism analysis. In a German replication cohort all exons were sequenced in 40 non-alcoholic CP cases and variant c.616G > A (p.V206M) was further analyzed by sequencing in 321 CP cases and 171 controls.
  
  
  RESULTS
  Sequencing of the entire coding region revealed four common variants: intronic variants c.23 + 78_110del, c.183-4C > A, c.1134 + 32C > A, and missense variant c.616G > A (p.V206M) which were found in linkage disequilibrium indicating a conserved haplotype. The distribution of the haplotype did not show a significant difference between patients and controls in the two cohorts. A synonymous variant c.1191C > A (p.P397=) and two intronic variants c.1248 + 9_20del and c.-10C > T were detected in single cases.
  
  
  CONCLUSIONS
  Our data show that SLC26A6 variants do not alter the risk for the development of CP.
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Anita
authors.initials: A
authors.lastname: Balázs
authors.affiliation: Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ruffert
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary; 2nd Department of Pediatrics, Comenius University Medical School, University Children's Hospital, Bratislava, Slovakia.
authors.forename: Eszter
authors.initials: E
authors.lastname: Hegyi
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Hritz
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Czakó
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Takács
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szepes
authors.affiliation: Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA 02118, USA.
authors.forename: Balázs Csaba
authors.initials: BC
authors.lastname: Németh
authors.affiliation: Szent György University Teaching Hospital of County Fejér, Székesfehérvár, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Gervain
authors.affiliation: Szent György University Teaching Hospital of County Fejér, Székesfehérvár, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Izbéki
authors.affiliation: Szent György University Teaching Hospital of County Fejér, Székesfehérvár, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Halász
authors.affiliation: Department of Surgery, University of Pécs, Hungary.
authors.forename: Dezső
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authors.lastname: Kelemen
authors.affiliation: Department of Interventional Gastroenterology, National Institute of Oncology, Budapest, Hungary.
authors.forename: Richárd
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authors.affiliation: Pándy Kálmán County Hopsital, Gyula, Hungary.
authors.forename: János
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authors.lastname: Novák
authors.affiliation: Pándy Kálmán County Hopsital, Gyula, Hungary.
authors.forename: Stefan
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authors.lastname: Crai
authors.affiliation: First Department of Medicine, University of Pécs, Hungary.
authors.forename: Anita
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authors.lastname: Illés
authors.affiliation: First Department of Medicine, University of Pécs, Hungary.
authors.forename: Áron
authors.initials: Á
authors.lastname: Vincze
authors.affiliation: Department of Anestesiology and Intensive Care, University of Szeged, Szeged, Hungary.
authors.forename: Zsolt
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authors.lastname: Molnár
authors.affiliation: Dr. Réthy Pál Hospital, Békéscsaba, Hungary.
authors.forename: Márta
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authors.lastname: Varga
authors.affiliation: Dr. Bugyi István Hospital, Szentes, Hungary.
authors.forename: Barnabás
authors.initials: B
authors.lastname: Bod
authors.affiliation: Department of Surgery, University of Szeged, Hungary.
authors.forename: Gyula
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authors.lastname: Farkas
authors.affiliation: B-A-Z County Hopspital and University Teaching Hospital, Miskolc, Hungary.
authors.forename: János
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authors.lastname: Sümegi
authors.affiliation: Department of Gastroenterology, Bács-Kiskun County Hospital, Kecskemét, Hungary.
authors.forename: Attila
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authors.lastname: Szepes
authors.affiliation: Department of Gastroenterology, Bács-Kiskun County Hospital, Kecskemét, Hungary.
authors.forename: Zsolt
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authors.lastname: Dubravcsik
authors.affiliation: Heim Pál Children's Hospital, Budapest, Hungary.
authors.forename: Natália
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authors.lastname: Lásztity
authors.affiliation: Heim Pál Children's Hospital, Budapest, Hungary.
authors.forename: Andrea
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authors.affiliation: Bajcsy-Zsilinszky Hospital, Budapest, Hungary.
authors.forename: József
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authors.lastname: Hamvas
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Faculty of Medicine, Budapest, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Andorka
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Faculty of Medicine, Budapest, Hungary.
authors.forename: Gábor
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authors.lastname: Veres
authors.affiliation: Institute of Surgery, University of Debrecen, Clinical Center, Debrecen Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szentkereszty
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rakonczay
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Maléth
authors.affiliation: Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA 02118, USA.
authors.forename: Miklós
authors.initials: M
authors.lastname: Sahin-Tóth
authors.affiliation: Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Rosendahl
authors.affiliation: First Department of Medicine, University of Szeged, Szeged, Hungary; MTA-SZTE Translational Gastroenterology Research Group, Szeged, Hungary. Electronic address: hegyi.peter@med.u-szeged.hu.
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D050500:Pancreatitis, Chronic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters
chemical_list: D005819:Genetic Markers; D026901:Membrane Transport Proteins; C439529:SLC26A6 protein, human; D000076988:Sulfate Transporters
keywords: Bicarbonate secretion; Candidate gene analysis; Chronic pancreatitis; Cl(−)-HCO(3)(−) exchanger; Genetic risk factor; Pancreatic duct