Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis.
Pancreatology
; 15(5): 508-513, 2015.
Article
in En
| MEDLINE
| ID: mdl-26372434
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Membrane Transport Proteins
/
Genetic Predisposition to Disease
/
Pancreatitis, Chronic
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Pancreatology
Journal subject:
ENDOCRINOLOGIA
/
GASTROENTEROLOGIA
Year:
2015
Document type:
Article
Affiliation country:
Hungria