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

作者：Balazs Anita; Ruffert Claudia; Hegyi Eszter; Hritz Istvan; Czako Laszlo; Takacs Tamas; Szepes Zoltan; Nemeth Balazs Csaba; Gervain Judit; Izbeki Ferenc; Halasz Adrienn; Kelemen Dezso; Szmola Richard; Novak Janos; Crai Stefan; Illes Anita; Vincze Aron; Molnar Zsolt; Varga Marta; Bod Barnabas; Farkas Gyula Jr; Suemegi Janos; Szepes Attila; Dubravcsik Zsolt; Lasztity Natalia; Parniczky Andrea; Hamvas Jozsef; Andorka Csilla; Veres Gabor; Szentkereszty Zsolt

来源：Pancreatology, 2015, 15(5): 508-513.

DOI：10.1016/j.pan.2015.08.008

• Candidate gene analysis
• Cl--HCO3- exchanger
• Pancreatic duct
• Chronic pancreatitis
• Genetic risk factor
• Bicarbonate secretion

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.

• 出版日期2015-10