Division of Gastroenterology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Pancreas. 2010 Nov;39(8):1215-9. doi: 10.1097/MPA.0b013e3181e2d4a0.
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.
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.
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.
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.
血小板衍生生长因子-β(PDGF-β)是通过激活胰腺星状细胞导致胰腺纤维化的增殖和基质合成的主要信号。复发性急性胰腺炎(RAP)似乎会使某些患者但不是所有患者易患慢性胰腺炎(CP)。我们检验了以下假说,即 2 种已知的 PDGF-β 多态性与从 RAP 进展为 CP 相关。我们还检验了 PDGF-β 多态性与环境风险因素(如酒精和吸烟)联合作用与 CP 相关的假说。
我们评估了 382 例 CP(n=176)和 RAP(n=206)患者以及 251 名对照者。使用单核苷酸多态性聚合酶链反应方法对 5'-UTR 中的 +286A/G(rs#1800818)和第一内含子中的 +1135A/C(rs#1800817)的血小板衍生生长因子-β多态性进行了基因分型,并通过 DNA 测序进行了确认。
在对照者和 RAP 以及 CP 患者中,位于+286 和+1135 位的 PDGF-β 多态性的基因型频率相似。在酒精和吸烟亚组的受试者中,RAP、CP 和对照者的基因型频率没有差异。
PDGF-β 基因的已知变异对促进或预防胰腺炎纤维化没有显著影响。需要进一步评估这一重要途径。