Paraoksonaz 1 gen polimorfizmleri (Q192r ve L55m) ve koroner yavaş akımla ilişkisi

Year 2023, Volume: 14 Issue: 3, 621 - 627, 30.09.2023

Arzu Akgün M. Yavuzkır Mehmet Akbulut

https://doi.org/10.18663/tjcl.1326512

Abstract

Amaç: Koroner yavaş akım (KYA), opak maddenin yavaş ilerlemesi ile karakterize anjiyografik bir antitedir ve aynı zamanda ve aterosklerozun erken bir göstergesi olduğu düşünülmektedir. İnsan paraoksonazı 1 (PON1), yüksek yoğunluklu lipoproteini (HDL) ve düşük yoğunluklu lipoproteini (LDL) oksidatif modifikasyonlardan korur. Paraoksonaz 1'in işleyişini etkileyen iki amino asit polimorfizmi (192Q/R ve 55L/M) vardır. PON1 iki genetik polimorfizmi ve koroner yavaş akım ile ilişkisini belirlemeyi amaçlıyoruz. Bildiğimiz kadarıyla çalışmamız PON1 gen polimorfizmleri (L55M ve Q192R) ile KYA ilişkisini değerlendiren ilk çalışmadır.
Gereç ve Yöntemler: Çalışmaya toplam 100 hasta dahil edildi ve normal koroner akım (NKA) ve KYA olmak üzere 2 gruba ayrıldı. rs854560 ve rs662 polimorfizmlerinin genomik dizileri polimeraz zincir reaksiyonu kullanılarak belirlendi. Araştırma protokolü Fırat Üniversitesi Kurumsal İnceleme Kurulu tarafından onaylanmıştır (Onay No:16).
Bulgular: Koroner yavaş akım grubunun yaş ortalaması 45,4±17 ve NKA grubunun 50,5±11 idi. Q ve R alellerini taşıma sıklığı açısından istatistiksel olarak fark vardı. Dual genotipler için, QQLM genotipi KYA grubunda daha yaygınken, QRLM genotipi NKA'de daha yaygındı. QQLM, RRLL, RRLM ve QRLM genotiplerine sahip hastalar ile sağlıklı bireyler arasında anlamlı fark bulundu.
Sonuçlar: Q aleli ile QQLM genotipi ve KYA arasında anlamlı bir ilişki bulduk ve bunların KYA için risk faktörleri olabileceğini düşündük. Ayrıca R aleli ile QRLM, RRLL ve RRLM genotiplerinin NKA grubunda daha yüksek olması ve istatistiksel olarak anlamlı bir ilişki bulunması bunların KYA için koruyucu faktörler olabileceğini düşündürdü.

Keywords

koroner yavaş akım, paraoksonaz, gen polimorfizmi, antioksidan

Supporting Institution

Fırat University Research Fund

Project Number

16

Paraoxonase 1 gene polymorphısms (Q192r and L55m) and assocıatıon wıth coronary slow flow

Abstract

Aim: Coronary slow flow (CSF) is an angiographic entity characterized by slow progression of opaque material and an early indicator of atherosclerosis. Paraoxonase 1 (PON1) protects high-density lipoprotein (HDL) and low-density lipoprotein (LDL) from oxidative modifications. PON 1 has two amino acid polymorphisms (192Q/R and 55L/M) and that affect its functioning. We aim to determine PON1 two genetic polymorphisms and relationship with CSF. As we know, our study is the first to assessment the relationship PON1 gene polymorphisms (L55M and Q192R) and CSF.
Materials and Methods: We included a total of 100 patients and 2 groups as normal coronary flow (NCF) and CSF. Genomic sequences of rs854560 and rs662 polymorphisms were determined using polymerase chain reaction. The research protocol was approved by Fırat University Institutional Review Board (Approval No:16).
Results: The mean age of CSF group was 45.4±17 and NCF group was 50.5±11 years. There was the statistically difference in terms of the frequency of carrying Q and R alleles. For dual genotypes, the QQLM genotype was more common in CSF group, whereas the QRLM genotype was more common in NCF. Significant differences were found between patients with QQLM, RRLL, RRLM and QRLM genotypes and healthy individuals.
Conslusion: We found a significant relationship between the Q allele and the QQLM genotype and CSF, and we thought that these may be risk factors for CSF. In addition, the fact that the R allele and QRLM, RRLL, and RRLM genotypes were higher in the NCF group and there was a statistically significant relationship suggested that these might be protective factors for CSF.

Keywords

coronary slow flow, paraoxonase, gene polymorphism, antioxidant

Project Number

16

References

• McPherson R, Tybjaerg-Hansen A. Genetics of coronary artery disease. Circ res. 2016;118(4):564-578.
• Hawkins BM, Stavrakis S, Rousan TA, Abu-Fadel M, Schechter E. Coronary slow flow-prevalence and clinical correlations. Circ J. 2012;76(4):936-942.
• Tambe AA, Demany MA, Zimmerman HA, Mascarenhas E. Angina pectoris and slow flow velocity of dye in coronary arteries- A new angiografic finding. Am Heart J. 1972;84(1):66-7.
• Türkoğlu C, Şeker T, Genç Ö, Yıldırım A, Topuz M. The relationship between H2FPEF score and coronary slow flow phenomenon. Turk Kardiyol Dern Ars. 2022;50(4):242-249.
• Wang X, Nie SP. The coronary slow flow phenomenon: characteristics, mechanisms and implications. Cardiovasc Diagn Ther. 2011;1(1):37-43.
• Kurtoğlu N, Akcay A, Dindar I. Usefulness of oral dipyridamole therapy for angiographic slow coronary artery flow. Am J Cardiol. 2001; 87(6):777-779.
• Beltrame JF, Limaye SB, Wuttke RD, Horowitz JD. Coronary hemodynamic and metabolic studies of the coronary slow flow phenomenon. Am Heart J. 2003;146(1):84-90.
• Primo-Parma SL, Sorenson RC, Teiber J, La Du BN. The Human serum Paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomic. 1996;33(3):498-509.
• Yazmín HD, Tovilla-Zarate CA, Juárez-Rojop IE 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.
• Sana A, Kanwal A. The role of paraoxonase 1 (PON1) gene polymorphisms in coronary artery disease: a systematic review and meta-analysis. Biochemical Genetics. 2021;59: 919-939.
• Kaman D, Ilhan N, Metin K, Akbulut M, Ustundag B. A preliminary study of human paraoxonase and PON1 L/M55-PON1 Q/R 192 polymorphisms in Turkish patients with coronary artery disease. Cell Biochem Funct. 2009;27(2):88-92.
• Aynacıoğlu A, Cascorbi I, Mrozikiewicz PM, Nacak M, Tapanyiğit EE, Roots I. Paraoxonase 1 Mutations in A Turkish Population. Toxicol Appl Pharmacol.1999; 157(3):174-177.
• Balcerzyk A, Zak I, Krauze J. Synergistic effects between Q192R polymorphism of paraoxonase 1 gene and some conventional risk factors in premature coronary artery disease. Arch Med Res. 2007;38(5):545-550.
• Sadr-Ameli MA, Saedi S, Saedi T, Madani M, Esmaeili M, Ghardoost B. Coronary slow flow: Benign or ominous? Anatol J Cardiol. 2015;15(7), 531-535.
• Aparicio A, Cuevas J, Morís C, Martín, M. Slow Coronary Blood Flow: Pathogenesis and Clinical Implications. Eur Cardiol. Review. 2022;17:e08.
• Cin VG, Pekdemir H, Camsar A, et al. Diffuse intimal thickening of coronary arteries in slow coronary flow. Jpn Heart J. 2003;44(6): 907–19.
• Catapano AL, Maggi FM, Tragni E. Low density lipoprotein oxidation, antioxidants, and atherosclerosis. Curr Opin Cardiol. 2000;15(5): 355-363.
• Dunet V, Ruiz J, Allenbach G, Izzo P, James RW, Prior JO. Effects of paraoxonase activity and gene polymorphism on coronary vasomotion. EJNMMI Res. 2011;1(1):27.
• International Consortium for Blood Pressure Genome-Wide Association Studies, Ehret GB, Munroe PB, et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011;478(7367):103-109.
• Kaur S, Bhatti GK, Vijayvergiya R, et al. Paraoxonase 1 Gene Polymorphisms (Q192R and L55M) Are Associated with Coronary Artery Disease Susceptibility in Asian Indians. Int J Diabetes Metab. 2018;21(1-4):38-47.
• Ko YL, Ko YS, Wang SM, et al. The Gln-Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan. Atherosclerosis.1998;141(2): 259-264.
• Sanghera DK, Saha N, Aston C, Kamboh MI. The codon 55 polymorphism in the Paraoxonase 1 gene is not associated with the risk of coronary heart disease in Asian Indians and Chinese. Atherosclerosis 1998;136(2): 217-223.
• Abelló D, Sancho E, Camps J, Joven J. Exploring the role of paraoxonases in the pathogenesis of coronary artery disease: a systematic review. Int J Mol Sci. 2014;15(11):20997–201010.
• Karakaya A, Ibis S, Kural T, Kose SK, Karakaya AE. Serum paraoxonase activity and phenotype distribution in Turkish subjects with coronary heart disease and its relationship to serum lipids and lipoproteins. Chem Biol Interact. 1999;118(3): 193-200.
• Aynacioglu AS, Kepekci Y. The human paraoxonase Gln-Argl92 (Q/R) polymorphism in turkish patients with coronary artery disease. Int J Cardiol. 2000;74(1): 33-37.
• Yildiz A, Gur M, Yilmaz R, et al. Association of paraoxonase activity and coronary blood flow. Atherosclerosis. 2008;197(1):257-263.
• Baysal SS, Koc S. Oxidant-Antioxidant balance in patients with coronary slow flow. Pak J Med Sci. 2019;35(3):786.