Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
PLoS One. 2011;6(5):e17805. doi: 10.1371/journal.pone.0017805. Epub 2011 May 24.
Human serum paraoxonase-1 (PON1) prevents oxidation of low density lipoprotein cholesterol (LDL-C) and hydrolyzes the oxidized form, therefore preventing the development of atherosclerosis. The polymorphisms of PON1 gene are known to affect the PON1 activity and thereby coronary artery disease (CAD) risk. As studies are lacking in North-West Indian Punjabi's, a distinct ethnic group with high incidence of CAD, we determined PON1 activity, genotypes and haplotypes in this population and correlated them with the risk of CAD.
METHODOLOGY/PRINCIPAL FINDINGS: 350 angiographically proven (≥ 70% stenosis) CAD patients and 300 healthy controls were investigated. PON1 activity was determined towards paraoxon (Paraoxonase; PONase) and phenylacetate (Arylesterase; AREase) substrates. In addition, genotyping was carried out by using multiplex PCR, allele specific oligonucleotide -PCR and PCR-RFLP methods and haplotyping was determined by PHASE software. The serum PONase and AREase activities were significantly lower in CAD patients as compared to the controls. All studied polymorphisms except L55M had significant effect on PONase activity. However AREase activity was not affected by them. In a logistic regression model, after adjustment for the conventional risk factors for CAD, QR (OR: 2.73 (1.57-4.72)) and RR (OR, 16.24 (6.41-41.14)) genotypes of Q192R polymorphism and GG (OR: 2.07 (1.02-4.21)) genotype of -162A/G polymorphism had significantly higher CAD risk. Haplotypes L-T-G-Q-C (OR: 3.25 (1.72-6.16)) and L-T-G-R-G (OR: 2.82 (1.01-7.80)) were also significantly associated with CAD.
In conclusion this study shows that CAD patients had lower PONase and AREase activities as compared to the controls. The coding Q192R polymorphism, promoter -162A/G polymorphism and L-T-G-Q-C and L-T-G-R-G haplotypes are all independently associated with CAD.
人血清对氧磷酶 1（PON1）可防止低密度脂蛋白胆固醇（LDL-C）氧化，并水解氧化形式，从而防止动脉粥样硬化的发展。PON1 基因的多态性已知会影响 PON1 活性，从而影响冠心病（CAD）的风险。由于在西北印度旁遮普邦人（一种具有高 CAD 发病率的独特族群）中缺乏研究，我们在该人群中测定了 PON1 活性、基因型和单倍型，并将其与 CAD 风险相关联。
方法/主要发现：对 350 名经血管造影证实（≥70%狭窄）的 CAD 患者和 300 名健康对照者进行了研究。测定了对氧磷（Paraoxonase；PONase）和苯乙酸酯（Arylesterase；AREase）底物的 PON1 活性。此外，采用多重 PCR、等位基因特异性寡核苷酸 -PCR 和 PCR-RFLP 方法进行基因分型，并用 PHASE 软件进行单倍型分析。与对照组相比，CAD 患者的血清 PONase 和 AREase 活性明显降低。除 L55M 外，所有研究的多态性均对 PONase 活性有显著影响。然而，AREase 活性不受它们的影响。在逻辑回归模型中，在校正 CAD 的传统危险因素后，QR（OR：2.73（1.57-4.72））和 RR（OR，16.24（6.41-41.14））基因型的 Q192R 多态性和-162A/G 多态性的 GG（OR：2.07（1.02-4.21））基因型与 CAD 风险显著增加相关。L-T-G-Q-C（OR：3.25（1.72-6.16））和 L-T-G-R-G（OR：2.82（1.01-7.80））单倍型也与 CAD 显著相关。
总之，本研究表明 CAD 患者的 PONase 和 AREase 活性明显低于对照组。编码 Q192R 多态性、启动子-162A/G 多态性以及 L-T-G-Q-C 和 L-T-G-R-G 单倍型均与 CAD 独立相关。
