阴离子型胰蛋白酶原基因G191R突变与胰腺炎发病的关系

The relation of cationic trypsinogen gene G191R mutation and pathogenesis of pancreatitis

目的 分析阴离子型胰蛋白酶原（PRSS2）基因G191R突变在急性胰腺炎（AP）和慢性胰腺炎（CP）患者中的发生率,探讨PRSS2基因突变对胰腺炎易感性的影响.方法 采集82例AP、73例CP及138例健康体检者的血液标本,提取基因组DNA.应用巢式PCR对PRSS2基因进行扩增.PCR产物用Hpy188Ⅲ酶切,行限制性片段长度多态性分析（RFLP）,部分产物测序验证.结果 PRSS2基因的巢式PCP产物长度为436 bp,RFLP2获得309 bp和127 bp两个片段,为RPSS2基因G191R突变（即GGA→AGA）所致.DNA测序证实PRSS2基因G191R突变.AP患者中5例发生RPSS2基因G191R突变,突变率为6.1％（5/82）,OR=0.682,95％ CI 0.231 ～ 2.010; CP患者突变率为1.4％ （1/73）,OR =0.145,95％ CI 0.019～1.145;健康对照组为8.7％ （12/138）.CP组的G191R突变率显著低于健康对照组（x2 =0.432,P=0.035）,而AP组与健康对照组的差异无统计学意义（x2=0.487,P=0.485）.结论 PRSS2基因G191R突变可促进阴离子型胰蛋白酶原的降解,降低慢性胰腺炎的发生率.

Objective To observe the prevalence of anionic trypsinogen （PRSS2） gene G191R mutation in patients with acute pancreatitis （AP） and chronic pancreatitis （CP）, and to investigate the effect of PRSS2 gene G191R mutation on susceptibility to pancreatitis. Methods The blood samples of 82 patients with acute pancreatitis, 73 patients with chronic pancreatitis and 138 healthy subjects were collected, and genomic DNA was extracted. Nest PCR were performed to amplify PRSS2 gene and restriction fragment length polymorphism （RFLP） was followed by using Hpy188III to distinguish the G191R mutation. DNA sequencing analysis was performed to confirm the mutation status. Results The size of nest PCR products was 436 bp. RFLP2 produced 309 bp and 127 bp fragments, which were resulted from PRSS2 gene G191R mutation （GGA --＊AGA）. DNA sequencing analysis of the PCR products further confirmed the PRSS2 gene G191R mutation. Five of eighty-two（6.1% ） patients with acute pancreatitis had PRSS2 gene G191R mutation （OR =0.682, 95% CI O. 231 ~2.010）; one of seventy-three（ 1.4% ） patients with chronic pancreatitis had the mutation （OR =0. 145, 95% CI O. 019 ~ 1. 145）, and the corresponding value in healthy group was 8.7% （12/138）. The G191R mutation rate in patients with chronic pancreatitis was significantly lower than that in healthy group （X2 =0. 432, P = 0.035）, but the G191R mutation rates were not signifieantly different between AP group and healthy group （ X2 = 0.487, P = 0.485）. Conclusions PRSS2 gene G191R mutation facilitates the degradationof anionic trypsin, and may reduce Ihe incidence of chronic, pancreatilis.