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北非人群中对氧磷酶1(PON1)基因多态性与急性冠脉综合征风险的关联

Association between Paraoxonase 1 (PON1) Polymorphisms and the Risk of Acute Coronary Syndrome in a North African Population.

作者信息

Bounafaa Abdelghani, Berrougui Hicham, Ghalim Noreddine, Nasser Boubker, Bagri Abdallah, Moujahid Abderrahmane, Ikhlef Souad, Camponova Pamela, Yamoul Najoua, Simo Olivier Kamtchueng, Essamadi Abdelkhalid, Khalil Abdelouahed

机构信息

Laboratory of Biochemistry & Neuroscience, Applied Biochemistry and Toxicology Team, Faculty of Sciences and Technology, Hassan First University, Settat, Morocco; Department of Medicine, Geriatrics Service, Faculty of Medicine and Biological Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada.

Department of Medicine, Geriatrics Service, Faculty of Medicine and Biological Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada; Department of Biology, Polydisciplinary Faculty, Sultan Moulay Sliman University, Beni-Mellal, Morocco.

出版信息

PLoS One. 2015 Aug 4;10(8):e0133719. doi: 10.1371/journal.pone.0133719. eCollection 2015.

Abstract

The purpose of the present study was to investigate the distribution of PON1 Q192R and L55M polymorphisms and activities in a North African population and to determine their association with cardiovascular complications. The prevalence of the QQ, QR, RR, LL, LM, and MM genotypes in the study population was 55.4%, 34.09%, 9.83%, 41.97%, 48.20%, and 9.83% respectively. The Q, R, L, and M alleles had a gene frequency of 0.755, 0.245, 0.67, and 0.33, respectively. The PON1 192 RR genotype was significantly more prevalent among ACS patients than among healthy subjects. There was a 4.33-fold increase in the risk of ACS in subjects presenting the PON1 192 RR genotype compared to those with the QQ genotype (OR=4.33; 95% CI=1.27-17.7). There was a significantly different distribution of PON1 L55M in the ACS patient groups (UA, STEMI, NSTEMI). Moreover, individuals presenting the PON1 55MM genotype present a higher risk for ACS than those with LL genotype (OR=3.69; 95% CI=1.61-11.80). Paraoxonase activities were significantly lower in coronary patients than in healthy subjects. The decrease in PON1 activity was inversely correlated with the number of concomitant risk factors for CVD (r=0.57, p<0.0001). The results of the present study suggested that the PON1 R and M alleles may play a role in the pathogenesis of cardiac ischemia in our North African population and that a decrease in PON1 activity may be a valuable marker for monitoring the development of the atherosclerosis process and the associated cardiovascular complications.

摘要

本研究的目的是调查北非人群中对氧磷酶1(PON1)Q192R和L55M多态性的分布及活性,并确定它们与心血管并发症的关联。研究人群中QQ、QR、RR、LL、LM和MM基因型的患病率分别为55.4%、34.09%、9.83%、41.97%、48.20%和9.83%。Q、R、L和M等位基因的基因频率分别为0.755、0.245、0.67和0.33。与健康受试者相比,急性冠状动脉综合征(ACS)患者中PON1 192 RR基因型的患病率显著更高。与QQ基因型的受试者相比,具有PON1 192 RR基因型的受试者发生ACS的风险增加了4.33倍(比值比[OR]=4.33;95%置信区间[CI]=1.27 - 17.7)。在ACS患者组(不稳定型心绞痛[UA]、ST段抬高型心肌梗死[STEMI]、非ST段抬高型心肌梗死[NSTEMI])中,PON1 L55M的分布存在显著差异。此外,与LL基因型的个体相比,具有PON1 55MM基因型的个体发生ACS的风险更高(OR=3.69;95% CI=1.61 - 11.80)。冠心病患者的对氧磷酶活性显著低于健康受试者。PON1活性的降低与心血管疾病(CVD)的伴随危险因素数量呈负相关(r=0.57,p<0.0001)。本研究结果表明,PON1的R和M等位基因可能在我们北非人群心脏缺血的发病机制中起作用,并且PON1活性的降低可能是监测动脉粥样硬化进程及相关心血管并发症发展的一个有价值的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d301/4524730/b4c12e56f4a2/pone.0133719.g001.jpg

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