International UNESCO Center for Health-Related Basic Sciences and Human Nutrition , Mashhad University of Medical Sciences , Mashhad - Irã.
Department of Biology , Faculty of Sciences , Ferdowsi University of Mashhad , Mashhad - Irã.
Arq Bras Cardiol. 2022 Oct;119(4):593-601. doi: 10.36660/abc.20210422.
It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity.
To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD).
A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant.
Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019).
The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.
已有研究表明，血清 PON1 水平升高可预防多种疾病。PON1 基因的一些单核苷酸多态性（SNP）已被报道与血清酶蛋白水平和活性有关。
探讨 PON1 基因 SNP 与血清对氧磷酶活性与冠心病（CAD）的关系。
共纳入 601 例接受冠状动脉造影的患者（包括狭窄程度>50%的患者 266 例和狭窄程度<30%的患者 335 例）。采用 ARMS-PCR 法检测 PON1 基因 rs662 和 rs840560 SNP，采用 PCR-RFLP 分析检测 rs705379 SNP。采用对氧磷作为底物测定血清对氧磷酶活性。p 值小于 0.05 为差异有统计学意义。
研究组之间血清对氧磷酶活性无显著差异。在校正年龄、性别、高血压、糖尿病和血脂异常后，rs662 的 GG 基因型和共显性模型与阳性血管造影呈正相关（分别为 OR=2.424，95%CI [1.123-5.233]，p<0.05，OR=1.663，95%CI [1.086-2.547]）。rs662 的 G 等位基因和 GG 变异、rs854560 的 A 等位基因和 AA 变异以及 rs705379 的 C 等位基因和 CC 变异均导致血清对氧磷酶活性升高。单体型分析表明，AGT 单体型在血管造影阴性组中更为常见。组间分析表明，rs662 的 A 等位基因与阳性血管造影组的对氧磷酶活性降低显著相关（p=0.019）。
rs662 单核苷酸多态性的 G 等位基因与 CAD 风险增加独立相关。
