Objetcive: Gene factors play an important role in coronary artery disease (CAD). Atherosclerosis is the most common process of developing CAD. Low density lipoprotein (LDL) oxidation has an essential role in the process of atherosclerosis. The paraoxonase 1 (PON1) enzyme that presents in the HDL structure inhibits LDL oxidation. A number of studies have been conducted around the world, investigating the relation between PON1 gene polymorphism and CAD. Different results have been obtained in various populations; therefore, these findings cannot be generalized to the Iranian population. Consequently, a comprehensive study of the prevalence of PON1 Q192R polymorphism is required. Material and Methods: In the present investigation, the study population consisted of 150 subjects, including 102 CAD patients and 48 healthy controls. The Q192R polymorphism of paraoxonase 1 was evaluated in general and also by ethnicity, employing the PCR-RFLP method. Results: In general, there was no significant difference (p>0.05) in the distribution of QQ, QR, and RR genotypes between patients and controls. In the study by ethnicity, in the Arab ethnic group, in patients with CAD, frequency of QQ genotype was significantly higher, while RR genotype was considerably lower than controls (p<0.05). Therefore, QQ genotype could be considered as a risk factor and RR genotype as a protective factor against CAD in the Arab race. Conclusion: The Q192R polymorphism of paraoxonase 1 in Arab ethnic group had a significant correlation with CAD. However, no overall association was found between this polymorphism and CAD.
Keywords: Q192R polymorphism of paraoxonase 1; coronary artery disease; Genetic difference
Amaç: Gen faktörleri koroner arter hastalığında (KAH) önemli rol oynar. Ateroskleroz KAH gelişiminin en yaygın sürecidir. Düşük yoğunluklu protein (LDL) oksidasyonunun ateroskleroz sürecinde önemli rolü vardır. Yüksek yoğunluklu protein (HDL) yapısında yer alan paraoksonaz 1 (PON1) enzimi LDL oksidasyonunu inhibe eder. Dünyada PON1 gen polimorfizmi ile KAH arasındaki ilişkiyi inceleyen çok sayıda çalışma yapılmıştır. Çeşitli populasyonlarda farklı sonuçlar elde edilmiştir; bu nedenle bu bulgular İran populasyonuna genellenemez. Sonuç olarak, PON1 Q192R polimorfizminin prevalansı ile ilgili kapsamlı bir çalışma yapılması gereklidir. Gereç ve Yöntemler: Bu araştırmada, çalışma populasyonu 150 olguyu içeriyordu (KAH olan 102 hasta ve 48 sağlıklı kontrol). Paraoksonazın Q192R polimorfizmi PCR-RFLP yöntemi kullanılarak genelde ve etnisiteye göre değerlendirildi. Bulgular: Genelde, hastalarla kontroller arasında QQ, QR ve RR genotiplerinin dağılımı açısından anlamlı fark yoktu (p>0.05). Etnisiteye göre ise Arap etnik grubunda KAH olanlarda QQ genotpinin sıklığı anlamlı olarak daha yüksekti, RR genotipi konrollere göre anlamlı olarak daha düşüktü (p<0.05). Bu nedenle, Arap toplumunda QQ genotipi bir risk faktörü olarak düşünülebilir ve RR genotipi koruyucu bir faktör olarak düşünülebilir. Sonuç: Arap etnik grubunda paraoksonaz 1?in Q192R polimorfizmi KAH ile anlamlı olarak korele idi. Fakat bu polimorfizm ile KAH arasında genel bir ilişki bulunmadı.
Anahtar Kelimeler: Q192R polimorfizmi; koroner arter hastalığı; genetik farklılık
- Krishnan MN. Coronary heart disease and risk factors in India-on the brink of an epidemic? Indian Heart J. 2012;64(4):364-7. [Crossref] [PubMed] [PMC]
- Firdaus M, Asbury JM, Reynolds DW. A new paradigm of cardiovascular risk factor modification. Vasc Health Risk Manag. 2005;1(2):101-9. [Crossref] [PubMed] [PMC]
- Yang C, Wang X, Ding H. Is coronary artery disease a multifactorial inherited disorder with a sex-influenced trait. Med Hypotheses. 2008;71(3):449-52. [Crossref] [PubMed]
- Sayols-Baixeras S, Lluís-Ganella C, Lucas G, Elosua R. Pathogenesis of coronary artery disease: focus on genetic risk factors and identification of genetic variants. Appl Clin Genet. 2014;7:15-32. [Crossref] [PubMed] [PMC]
- Ghattas A, Griffiths HR, Devitt A, Lip GY, Shantsila E. Monocytes in coronary artery disease and atherosclerosis: where are we now? J Am Coll Cardiol. 2013;62(17):1541-51. [Crossref] [PubMed]
- Podrez EA. Antioxidant properties of high‐density lipoprotein and atherosclerosis. Clin Exp Pharmacol Physiol. 2010; 7(7):719-25. [Crossref] [PubMed] [PMC]
- Ansell BJ, Fonarow GC, Fogelman AM. The paradox of dysfunctional high-density lipoprotein. Curr Opin Lipidol. 2007;18(4):427-34. [Crossref] [PubMed]
- Rosenblat M, Vaya J, Shih D, Aviram M. Paraoxonase 1 (PON1) enhances HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter in association with increased HDL binding to the cells: a possible role for lysophosphatidylcholine. Atherosclerosis. 2005;179(1):69-77. [Crossref] [PubMed]
- Chistiakov DA, Melnichenko AA, Orekhov AN, Bobryshev YV. Paraoxonase and atherosclerosis-related cardiovascular diseases. Biochimie. 2017;132:19-27. [Crossref] [PubMed]
- Birjmohun RS, Vergeer M, Stroes ES, Sandhu MS, Ricketts SL, Tanck MW, et al. Both paraoxonase-1 genotype and activity do not predict the risk of future coronary artery disease; the EPIC-Norfolk Prospective Population Study. PloS One. 2009;4(8):e6809. [Crossref] [PubMed] [PMC]
- Hernández-Díaz Y, Tovilla-Zárate CA, Juárez-Rojop IE, González-Castro TB, Rodríguez-Pérez C, López-Narváez, et al. Effects of paraoxonase 1 gene polymorphisms on heart diseases: systematic review and meta-analysis of 64 case-control studies. Medicine (Baltimore). 2016;95(44):e5298. [Crossref] [PubMed] [PMC]
- Taşkiran P, Cam SF, Sekuri C, Tüzün N, Alioğlu E, Altıntaş N, et al. The relationship between paraoxanase gene Leu-Met (55) and Gln-Arg (192) polymorphisms and coronary artery disease. Turk Kardiyol Dern Ars. 2009;37(7):473-8.
- Lawlor DA, Day IN, Gaunt TR, Hinks LJ, Briggs PJ, Kiessling M, et al. The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis. BMC Genet. 2004;5(1):17. doi:10.1186/1471-2156-5-17. [Crossref] [PubMed] [PMC]
- Zhao Y, Ma Y, Fang Y, Liu L, Wu S, Fu D, et al. Association between PON1 activity and coronary heart disease risk: a meta-analysis based on 43 studies. Mol Genet Metab. 2012;105(1):141-8. [Crossref] [PubMed]
- Bhattacharyya T, Nicholls SJ, Topol EJ, Zhang R, Yang X, Schmitt D, et al. Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. JAMA. 2008;299(11):1265-76. [Crossref] [PubMed] [PMC]
- Ozkök E, Aydin M, Babalik E, Ozbek Z, Ince N, Kara I. Combined impact of matrix metalloproteinase-3 and paraoxonase 1 55/192 gene variants on coronary artery disease in Turkish patients. Med Sci Monit. 2008;14(10):CR536-42.
- Agrawal S, Tripathi G, Prajnya R, Sinha N, Gilmour A, Bush L, et al. Paraoxonase 1 GENE polymorphisms contribute to coronary artery disease risk. Indian J Med Sci. 2009;63(8):335-44. [Crossref] [PubMed]
- Hassan MA, Al-Attas OS, Hussain T, Al-Daghri NM, Alokail MS, Mohammed AK, et al. The Q192R polymorphism of the paraoxonase 1 gene is a risk factor for coronary artery disease in Saudi subjects. Mol Cell Biochem. 2013;380(1-2):121-8. [Crossref] [PubMed]
- Vaisi-Raygani A, Ghaneialvar H, Rahimi Z, Tavilani H, Pourmotabbed T, Shakiba E, et al. Paraoxonase Arg 192 allele is an independent risk factor for three-vessel stenosis of coronary artery disease. Mol Biol Rep. 2011;38(8):5421-8. [Crossref] [PubMed]
.: İşlem Listesi