Verlaan Mariette, Harbers Erik G A, Pap Akos, Jansen Jan B M J, Peters Wilbert H M, Drenth Joost P H
Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Mol Diagn. 2005;9(1):9-15. doi: 10.2165/00066982-200509010-00002.
The cause of chronic pancreatitis (CP) remains unknown. However, oxidative stress might play a role since recent animal studies have demonstrated that oxygen-free radicals contribute to the pathogenesis of experimental pancreatitis. Human serum paraoxonase (PON1) is an antioxidant enzyme that protects against cellular damage from oxidative stress. Genetic variations resulting in variable activity rates of this enzyme, are of toxicological and physiological importance.
We investigated whether genetic polymorphisms of the PON1 gene modify the risk for CP.
DNA samples were obtained from 236 adult CP patients of hereditary (n = 23), alcoholic (n = 137), or idiopathic (n = 76) origin. DNA from 113 healthy controls and from 93 alcoholic controls were analyzed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms (L55M and Q192R) in PON1 were determined by PCR, followed by restriction fragment length polymorphism analyses in all subjects.
The frequencies of the PON1-55 alleles did not differ between CP patients and healthy controls. However, the PON1-192Q allele was significantly more common in idiopathic CP patients (OR : 1.5, 95% CI 1.02, 2.5) compared with healthy controls.
These data suggest that the PON1-192Q allele, resulting in partly deficient antioxidant and detoxification activity of this enzyme, might be a risk factor for idiopathic CP in Caucasians.
慢性胰腺炎(CP)的病因尚不清楚。然而,氧化应激可能起作用,因为最近的动物研究表明,氧自由基参与实验性胰腺炎的发病机制。人血清对氧磷酶(PON1)是一种抗氧化酶,可保护细胞免受氧化应激损伤。导致该酶活性率变化的基因变异具有毒理学和生理学意义。
我们研究了PON1基因的多态性是否会改变CP的发病风险。
DNA样本取自236例成年CP患者,分别为遗传性(n = 23)、酒精性(n = 137)或特发性(n = 76)。分析了113例健康对照和93例酒精性对照的DNA进行比较。患者和对照均为白种人。通过PCR测定PON1基因的多态性(L55M和Q192R),随后对所有受试者进行限制性片段长度多态性分析。
CP患者和健康对照之间PON1 - 55等位基因的频率没有差异。然而,与健康对照相比,PON1 - 192Q等位基因在特发性CP患者中显著更常见(比值比:1.5,95%可信区间1.02,2.5)。
这些数据表明,导致该酶抗氧化和解毒活性部分缺陷的PON1 - 192Q等位基因可能是白种人特发性CP的一个风险因素。