Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis
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),...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2015
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| Sorozat: | PANCREATOLOGY
15 No. 5 |
| doi: | 10.1016/j.pan.2015.08.008 |
| mtmt: | 2954565 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/11478 |
| Tartalmi kivonat: | 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. |
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| Terjedelem/Fizikai jellemzők: | 508-513 |
| ISSN: | 1424-3903 |