Are genetic variants in the platelet-derived growth factor [beta] gene associated with chronic pancreatitis?

Abstract

Objectives: 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.

Figure 1

Figure 1a: Genotype distribution +286 A/G polymorphism among RAP and CP patients and controls RAP, Recurrent acute pancreatitis. CP, Chronic pancreatitis. Figure 1b: Genotype distribution +1135 A/C polymorphism among RAP and CP patients and controls RAP, Recurrent acute pancreatitis. CP, Chronic pancreatitis.

Figure 1

Figure 1a: Genotype distribution +286 A/G polymorphism among RAP and CP patients and controls RAP, Recurrent acute pancreatitis. CP, Chronic pancreatitis. Figure 1b: Genotype distribution +1135 A/C polymorphism among RAP and CP patients and controls RAP, Recurrent acute pancreatitis. CP, Chronic pancreatitis.