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

Pancreatology. 2015 Sep-Oct;15(5):508-513. doi: 10.1016/j.pan.2015.08.008. Epub 2015 Sep 1.

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(3)(−) exchanger; Genetic risk factor; Pancreatic duct.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Mutation
  • Pancreatitis, Chronic / genetics*
  • Polymorphism, Restriction Fragment Length
  • Sequence Analysis, DNA
  • Sulfate Transporters

Substances

  • Genetic Markers
  • Membrane Transport Proteins
  • SLC26A6 protein, human
  • Sulfate Transporters