Are genetic variants in the platelet-derived growth factor [beta] gene associated with chronic pancreatitis?
OBJECTIVE
Platelet-derived growth factor [beta] (PDGF-[beta]) is a major signal in proliferation and matrix synthesis through activated pancreatic stellate cells, leading to fibrosis of the pancreas. Recurrent acute pancreatitis (RAP) seems to predispose to chronic pancreatitis (CP) in some patients but not others. We tested the hypothesis that 2 known PDGF-[beta] polymorphisms are associated with progression from RAP to CP. We also tested the hypothesis that PDGF-[beta] polymorphisms in combination with environmental risk factors such as alcohol and smoking are associated with CP.


METHODS
Three hundred eighty-two patients with CP (n = 176) and RAP (n = 206) and 251 controls were evaluated. Platelet-derived growth factor [beta] polymorphisms +286 A/G (rs#1800818) seen in 5'-UTR and +1135 A/C (rs#1800817) in first intron were genotyped using single-nucleotide polymorphism polymerase chain reaction approach and confirmed by DNA sequencing.


RESULTS
The genotypic frequencies for PDGF-[beta] polymorphisms in positions +286 and +1135 were found to be similar in controls and patients with RAP and CP. There was no difference in genotypic frequencies among RAP, CP, and controls in subjects in the alcohol and smoking subgroups.


CONCLUSIONS
Known variations in the PDGF-[beta] gene do not have a significant effect on promoting or preventing fibrogenesis in pancreatitis. Further evaluation of this important pathway is warranted.
Muddana
Venkata
V
Division of Gastroenterology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Park
James
J
Lamb
Janette
J
Yadav
Dhiraj
D
Papachristou
Georgios I
GI
Hawes
Robert H
RH
Brand
Randall
R
Slivka
Adam
A
Whitcomb
David C
DC
D020121:5' Untranslated Regions / Q000235:genetics; D000208:Acute Disease; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000235:genetics* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
D020121:5' Untranslated Regions; D020574:Proto-Oncogene Proteins c-sis