Relationship of human paraoxonase-1 serum activity and genotype with atherosclerosis in individuals from the Deep South.
Relationship of human paraoxonase-1 serum activity and genotype with atherosclerosis in individuals from the Deep South.
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DOI：
10.1097/fpc.0b013e32834cebc6
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发表时间：
2011-12
影响因子：
2.6
通讯作者：
Chambers JE
中科院分区：
文献类型：
--
作者：
Coombes RH;Crow JA;Dail M;Chambers HW;Wills RW;Barry D. Bertolet for CARe;Chambers JE
对氧磷酶1（PON1）在肝脏中合成，并与血液中的高密度脂蛋白（HDL）颗粒结合。PON1通过代谢促动脉粥样硬化的氧化脂质来防止动脉粥样硬化的发展。美国东南部（不包括佛罗里达）的心血管疾病年龄调整死亡率最高。目前的研究确定了PON1状态与美国东南部个体动脉粥样硬化（ATH）的相关性。从密西西比东北部的一家心脏病诊所招募了80名非洲裔美国人（40名男性，40名女性）和120名白人（60名男性，60名女性）。以二氮氧磷、对氧磷和醋酸苯酯为底物测定血清PON1活性。还确定了每个个体的PON1192基因型。多变量logistic回归模型被用来确定研究人群中ATH的临床特征、血清PON1活性和PON1192基因型之间的关系。核心模型由年龄、性别、吸烟史、高血压和LDL胆固醇组组成。核心模型的最大重标度广义r2值为0.35。通过PhAc水解评估的PON1活性的添加是PON1酶活性的唯一测量，以向核心模型添加显著信息（p= 0.0317），最大重新缩放的广义r2值增加至0.37。增加PON1活性与降低ATH几率相关。PON1192基因型与ATH无显著相关性。在一组非裔美国人和高加索南方人中，通过PhAc水解评估的PON1活性增加与ATH几率降低相关。
Paraoxonase 1 (PON1) is synthesized in the liver and bound to high density lipoprotein (HDL) particles in blood. PON1 protects against the development of atherosclerosis by metabolizing pro-atherogenic oxidized lipids. The Southeastern United States (excluding Florida) has the country's highest age-adjusted mortality rate from cardiovascular disease. The current study determines the association of PON1 status with atherosclerosis (ATH) in individuals from the Southeastern United States. Eighty African Americans (40 male, 40 female) and 120 Caucasians (60 male, 60 female) were enrolled from a cardiology practice in northeastern Mississippi. Serum PON1 activities were determined using diazoxon, paraoxon, and phenyl acetate (PhAc) as substrates. The PON1192 genotype of each individual was also determined. A multivariable logistic regression model was developed to identify the associations of clinical characteristics, serum PON1 activity, and PON1192 genotype of the study population with ATH. A core model consisting of age, gender, history of smoking, hypertension, and LDL-cholesterol group was constructed. The maximum-rescaled generalized r2 value for the core model was 0.35. Addition of PON1 activity assessed by PhAc hydrolysis was the only measure of PON1 enzymatic activity to add significant information to the core model (p= 0.0317) with the maximum-rescaled generalized r2 value increasing to 0.37. Increasing PON1 activity was associated with decreased odds of ATH. The PON1192 genotype was not significantly associated with ATH. Increasing PON1 activity assessed by the hydrolysis of PhAc is associated with decreased odds of ATH in a group of African American and Caucasian Southerners.