Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis

Anita Balázs, Claudia Ruffert, Eszter Hegyi, I. Hritz, L. Czakó, T. Takács, Zoltán Szepes, Balázs Csaba Németh, Judit Gervain, F. Izbéki, Adrienn Halász, Dezso Kelemen, R. Szmola, János Novák, Stefan Crai, Anita Illés, A. Vincze, Z. Molnár, Márta Varga, Barnabás Bod & 15 others Gyula Farkas, János Sümegi, Attila Szepes, Zsolt Dubravcsik, Natália Lásztity, Andrea Párniczky, József Hamvas, Csilla Andorka, G. Verès, Zsolt Szentkereszty, Z. Rakonczay, József Maléth, Miklós Sahin-Tóth, Jonas Rosendahl, P. Hegyi

Research output: Article

3 Citations (Scopus)

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. Conclusion Our data show that SLC26A6 variants do not alter the risk for the development of CP.

Original languageEnglish
Pages (from-to)508-513
Number of pages6
JournalPancreatology
Volume15
Issue number5
DOIs
Publication statusPublished - szept. 1 2015

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Chronic Pancreatitis
Bicarbonates
Anions
Haplotypes
Cystic Fibrosis Transmembrane Conductance Regulator
Pancreatic Diseases
Chloride Channels
Linkage Disequilibrium
Restriction Fragment Length Polymorphisms
Registries
Pancreas
Exons
Mutation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Hepatology

Cite this

Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis. / Balázs, Anita; Ruffert, Claudia; Hegyi, Eszter; Hritz, I.; Czakó, L.; Takács, T.; Szepes, Zoltán; Németh, Balázs Csaba; Gervain, Judit; Izbéki, F.; Halász, Adrienn; Kelemen, Dezso; Szmola, R.; Novák, János; Crai, Stefan; Illés, Anita; Vincze, A.; Molnár, Z.; Varga, Márta; Bod, Barnabás; Farkas, Gyula; Sümegi, János; Szepes, Attila; Dubravcsik, Zsolt; Lásztity, Natália; Párniczky, Andrea; Hamvas, József; Andorka, Csilla; Verès, G.; Szentkereszty, Zsolt; Rakonczay, Z.; Maléth, József; Sahin-Tóth, Miklós; Rosendahl, Jonas; Hegyi, P.

In: Pancreatology, Vol. 15, No. 5, 01.09.2015, p. 508-513.

Research output: Article

Balázs, A, Ruffert, C, Hegyi, E, Hritz, I, Czakó, L, Takács, T, Szepes, Z, Németh, BC, Gervain, J, Izbéki, F, Halász, A, Kelemen, D, Szmola, R, Novák, J, Crai, S, Illés, A, Vincze, A, Molnár, Z, Varga, M, Bod, B, Farkas, G, Sümegi, J, Szepes, A, Dubravcsik, Z, Lásztity, N, Párniczky, A, Hamvas, J, Andorka, C, Verès, G, Szentkereszty, Z, Rakonczay, Z, Maléth, J, Sahin-Tóth, M, Rosendahl, J & Hegyi, P 2015, 'Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis', Pancreatology, vol. 15, no. 5, pp. 508-513. https://doi.org/10.1016/j.pan.2015.08.008
Balázs, Anita ; Ruffert, Claudia ; Hegyi, Eszter ; Hritz, I. ; Czakó, L. ; Takács, T. ; Szepes, Zoltán ; Németh, Balázs Csaba ; Gervain, Judit ; Izbéki, F. ; Halász, Adrienn ; Kelemen, Dezso ; Szmola, R. ; Novák, János ; Crai, Stefan ; Illés, Anita ; Vincze, A. ; Molnár, Z. ; Varga, Márta ; Bod, Barnabás ; Farkas, Gyula ; Sümegi, János ; Szepes, Attila ; Dubravcsik, Zsolt ; Lásztity, Natália ; Párniczky, Andrea ; Hamvas, József ; Andorka, Csilla ; Verès, G. ; Szentkereszty, Zsolt ; Rakonczay, Z. ; Maléth, József ; Sahin-Tóth, Miklós ; Rosendahl, Jonas ; Hegyi, P. / Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis. In: Pancreatology. 2015 ; Vol. 15, No. 5. pp. 508-513.
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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. Conclusion Our data show that SLC26A6 variants do not alter the risk for the development of CP.",
keywords = "Bicarbonate secretion, Candidate gene analysis, Chronic pancreatitis, Cl-HCO exchanger, Genetic risk factor, Pancreatic duct",
author = "Anita Bal{\'a}zs and Claudia Ruffert and Eszter Hegyi and I. Hritz and L. Czak{\'o} and T. Tak{\'a}cs and Zolt{\'a}n Szepes and N{\'e}meth, {Bal{\'a}zs Csaba} and Judit Gervain and F. Izb{\'e}ki and Adrienn Hal{\'a}sz and Dezso Kelemen and R. Szmola and J{\'a}nos Nov{\'a}k and Stefan Crai and Anita Ill{\'e}s and A. Vincze and Z. Moln{\'a}r and M{\'a}rta Varga and Barnab{\'a}s Bod and Gyula Farkas and J{\'a}nos S{\"u}megi and Attila Szepes and Zsolt Dubravcsik and Nat{\'a}lia L{\'a}sztity and Andrea P{\'a}rniczky and J{\'o}zsef Hamvas and Csilla Andorka and G. Ver{\`e}s and Zsolt Szentkereszty and Z. Rakonczay and J{\'o}zsef Mal{\'e}th and Mikl{\'o}s Sahin-T{\'o}th and Jonas Rosendahl and P. Hegyi",
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TY - JOUR

T1 - Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis

AU - Balázs, Anita

AU - Ruffert, Claudia

AU - Hegyi, Eszter

AU - Hritz, I.

AU - Czakó, L.

AU - Takács, T.

AU - Szepes, Zoltán

AU - Németh, Balázs Csaba

AU - Gervain, Judit

AU - Izbéki, F.

AU - Halász, Adrienn

AU - Kelemen, Dezso

AU - Szmola, R.

AU - Novák, János

AU - Crai, Stefan

AU - Illés, Anita

AU - Vincze, A.

AU - Molnár, Z.

AU - Varga, Márta

AU - Bod, Barnabás

AU - Farkas, Gyula

AU - Sümegi, János

AU - Szepes, Attila

AU - Dubravcsik, Zsolt

AU - Lásztity, Natália

AU - Párniczky, Andrea

AU - Hamvas, József

AU - Andorka, Csilla

AU - Verès, G.

AU - Szentkereszty, Zsolt

AU - Rakonczay, Z.

AU - Maléth, József

AU - Sahin-Tóth, Miklós

AU - Rosendahl, Jonas

AU - Hegyi, P.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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. Conclusion Our data show that SLC26A6 variants do not alter the risk for the development of CP.

AB - 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. Conclusion Our data show that SLC26A6 variants do not alter the risk for the development of CP.

KW - Bicarbonate secretion

KW - Candidate gene analysis

KW - Chronic pancreatitis

KW - Cl-HCO exchanger

KW - Genetic risk factor

KW - Pancreatic duct

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U2 - 10.1016/j.pan.2015.08.008

DO - 10.1016/j.pan.2015.08.008

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VL - 15

SP - 508

EP - 513

JO - Pancreatology

JF - Pancreatology

SN - 1424-3903

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