Background Oxidative stress such as low-density lipoprotein （LDL） oxidation is thought to be an important mechanism in Alzheimer＇s disease （AD）. Paraoxonase 1 （PON1）, an enzyme located on high-density lipoprote...Background Oxidative stress such as low-density lipoprotein （LDL） oxidation is thought to be an important mechanism in Alzheimer＇s disease （AD）. Paraoxonase 1 （PON1）, an enzyme located on high-density lipoprotein, can prevent LDL from oxidation to some extent. It is also a potent cholinesterase inhibitor and an arylesterase, combating organophosphate poisoning and metabolization of environmental neurotoxins which might be responsible for neurodegeneration with aging.We evaluated the association of Gln192Arg polymorphism in the PON1 gene with AD in a Chinese Han ethnic population. Methods Patients and age-matched controls were recruited from outpatient clinics and a population-based epidemiological survey, respectively. Gln192Arg polymorphism in the PON1 gene was detected by allele-specific PCR technique in 521 patients with AD and 578 healthy controls. Results The presence of at least one of PON1 R alleles （Q/R or R/R） was lower in AD patients than in the controls （82.7% vs 87.4%; χ^2 = 4.68, P = 0.03）. PON1 gene R allele frequency was lower in AD patients than in the controls （60.7% vs 64.7%; χ^2=3.85, P = 0.05）. One-way ANOVA showed that PON1 genotype had no effect on the age of onset for developing AD. Logistic regression analysis demonstrated the age and sex-adjusted odds ratio （OR） for the risk of AD in PON1 of PON1 R allele carriers was 0.71 （P = 0.044, 95%CI, 0.51 - 0.99）.Conclusion Our results indicate that Gln192Arg polymorphism in the PON1 gene is associated with AD, and PON1 R allele might be a protective factor for AD in a Chinese Han ethnic population.展开更多
基金This work was supported by grants from the National Committee on Science and Technology, (No. 96-096-05-01) China Medical Board in New York (No. CMB 99-699).
文摘Background Oxidative stress such as low-density lipoprotein （LDL） oxidation is thought to be an important mechanism in Alzheimer＇s disease （AD）. Paraoxonase 1 （PON1）, an enzyme located on high-density lipoprotein, can prevent LDL from oxidation to some extent. It is also a potent cholinesterase inhibitor and an arylesterase, combating organophosphate poisoning and metabolization of environmental neurotoxins which might be responsible for neurodegeneration with aging.We evaluated the association of Gln192Arg polymorphism in the PON1 gene with AD in a Chinese Han ethnic population. Methods Patients and age-matched controls were recruited from outpatient clinics and a population-based epidemiological survey, respectively. Gln192Arg polymorphism in the PON1 gene was detected by allele-specific PCR technique in 521 patients with AD and 578 healthy controls. Results The presence of at least one of PON1 R alleles （Q/R or R/R） was lower in AD patients than in the controls （82.7% vs 87.4%; χ^2 = 4.68, P = 0.03）. PON1 gene R allele frequency was lower in AD patients than in the controls （60.7% vs 64.7%; χ^2=3.85, P = 0.05）. One-way ANOVA showed that PON1 genotype had no effect on the age of onset for developing AD. Logistic regression analysis demonstrated the age and sex-adjusted odds ratio （OR） for the risk of AD in PON1 of PON1 R allele carriers was 0.71 （P = 0.044, 95%CI, 0.51 - 0.99）.Conclusion Our results indicate that Gln192Arg polymorphism in the PON1 gene is associated with AD, and PON1 R allele might be a protective factor for AD in a Chinese Han ethnic population.
