Paraoxonase 1-192Q allele is a risk factor for idiopathic chronic pancreatitis.

Mariette Verlaan, Erik G A Harbers, Akos Pap, Jan B M J Jansen, Wilbert H M Peters, Joost P H Drenth
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引用次数: 7

Abstract

Background: 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.

Aim: We investigated whether genetic polymorphisms of the PON1 gene modify the risk for CP.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

对氧磷酶1-192Q等位基因是特发性慢性胰腺炎的危险因素。
背景: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,氧自由基有助于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,保护细胞免受氧化应激损伤。遗传变异导致这种酶的活性率变化,具有毒理学和生理学的重要性。目的:研究PON1基因的遗传多态性是否改变CP的风险。材料和方法:236例成年CP患者的DNA样本来自遗传(n = 23)、酒精(n = 137)和特发性(n = 76)来源。分析了113名健康对照者和93名酗酒对照者的DNA进行比较。患者和对照组均为白种人。采用PCR检测PON1基因的遗传多态性(L55M和Q192R),并对所有受试者进行限制性内切片段长度多态性分析。结果:CP患者与健康对照间PON1-55等位基因的频率无显著差异。然而,与健康对照相比,PON1-192Q等位基因在特发性CP患者中更为常见(OR: 1.5, 95% CI 1.02, 2.5)。结论:这些数据表明,PON1-192Q等位基因导致该酶部分缺乏抗氧化和解毒活性,可能是高加索人特发性CP的一个危险因素。
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