Mutational analysis of the gene encoding the zymogen granule membrane glycoprotein 2 (GP2) in patients with chronic pancreatitis.
OBJECTIVE
Premature activation of pancreatic digestive enzymes is considered as a major factor in the pathogenesis of pancreatitis. Genetic alterations of different pancreatic zymogens or their inhibitors have been associated with chronic pancreatitis (CP).


METHODS
We sequenced all 12 GP2 exons in 380 German CP patients and in 182 German control subjects. In addition, we analyzed exon 3 of GP2 in 803 further CP patients and 1780 controls originating from Germany, the Netherlands, and India by targeted DNA sequencing.


RESULTS
We detected 12 nonsynonymous and 6 synonymous exonic variants. All nonsynonymous changes with exception of c.220C>T (p.R74X) and c.502_503delG (p.G168fsX174) in exon 3 and c.541C>T (p.R181X) in exon 4 were missense mutations and predominantly located in exon 3. All nonsynonymous variants were found in single cases only, with exception of 2 alterations, c.355A>G (p.M119V) and c.409G>A (p. A137T), both located in exon 3. To elucidate the role of these 2 exon 3 variants, we investigated additional patients and controls. The frequency of these variants was similar between patients and controls regardless of ethnic background or cause of CP.


CONCLUSIONS
Our data suggest that GP2 alterations do not alter the risk for the development of CP.
Witt
Heiko
H
Department of Hepatology and Gastroenterology, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany. heiko.witt@lrz.tum.de
Rosendahl
Jonas
J
te Morsche
René H M
RH
Santhosh
Sundaresan
S
Chacko
Ashok
A
Schulz
Hans-Ulrich
HU
Landt
Olfert
O
Teich
Niels
N
Keim
Volker
V
Mössner
Joachim
J
Gress
Thomas M
TM
Ockenga
Johann
J
Schmidt
Hartmut
H
Kovacs
Peter
P
Blüher
Matthias
M
Stumvoll
Michael
M
Kage
Andreas
A
Groneberg
David Alexander
DA
Jansen
Jan B M J
JB
Nickel
Renate
R
Drenth
Joost P H
JP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D058851:GPI-Linked Proteins; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D007194:India; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D009426:Netherlands; D050500:Pancreatitis, Chronic / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
C489339:GP2 protein, human; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins