Mutations in the human paraoxonase 1 gene: frequencies, allelic linkages, and association with coronary artery disease

被引:43
作者
Cascorbi, I
Laule, M
Mrozikiewicz, PM
Mrozikiewicz, A
Andel, C
Baumann, G
Roots, I
Stangl, K
机构
[1] Humboldt Univ, Univ Klinikum Charite, Inst Clin Pharmacol, D-10098 Berlin, Germany
[2] Humboldt Univ, Univ Klinikum Charite, Dept Med 1, D-10098 Berlin, Germany
[3] Univ Sch Med, Inst Clin Pharmacol, Poznan, Poland
来源
PHARMACOGENETICS | 1999年 / 9卷 / 06期
关键词
CAD; lipid oxidation; PON; atherosclerosis;
D O I
10.1097/00008571-199912000-00010
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Oxidative damage is a major cause of atherosclerosis, Since human paraoxonase has been postulated as a factor which plays a role in protection from low density lipoprotein oxidation, recent studies have dealt with the impact of hereditary PON1 gene polymorphisms as risk factors for corollary artery disease (CAD), The results from these studies are conflicting, in a case-control study, 1000 Caucasian patients with angiographically confirmed CAD were recruited and matched by age and gender to 1000 control individuals, PON1 mutations in codons 55 and 192 were evaluated by polymerase chain reaction-restriction fragment length polymorphism and allocated to defined haplotypes *1 (55L/192Q), *2 (55L/192R), and *3 (55M/192Q). Frequency of PON1 genotypes without any mutation (PON1*1/*1, wild-type) in CAD cases was 16.9% versus 17.1% in control individuals. PON1*2/*2 showed a frequency of 6.6% versus 7.3% (P = 0.68 compared to wild-type), and PON1*3/3 occurred in 11.8% in CAD cases versus 10.3% among control individuals (P = 0.40). There was also no difference in the distribution of carriers heterozygous for *2 or *3 among cases and control individuals. A haplotype containing both mutations 55M and 192R was not observed. None of the investigated genotypes demonstrated association with early manifestation, severity of disease, acute coronary syndromes, or myocardial infarction. Logistic regression analysis with adjustment for age, gender, diabetes, hypertension, hypercholesterolemia and smoking revealed no evidence of increased coronary risk associated with PON1 genotypes, These results suggest that PON1 polymorphisms are not major genetic determinants of CAD. Pharmacogenetics 9:755-761 (C) 1999 Lippincott Williams & Wilkins.
引用
收藏
页码:755 / 761
页数:7
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