Iranian Journal of Medical Sciences

Document Type : Original Article(s)

Authors

1 Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Cardiovascular Research Center, Non-Communicable Diseases Research Institute, Afshar Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Center for Healthcare Data Modeling, Departments of Biostatistics and Epidemiology, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

5 Department of Medical Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, BP634, F8916978477 Yazd, Iran

6 Mother and Newborn Health Research Center, Shahid Sadoughi Hospital, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

7 Division of Genetics, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Biotechnology, University of Isfahan, Isfahan, Iran

8 Dr. Mazaheri’s Medical Genetics Lab, Yazd, Iran

10.30476/ijms.2023.98201.3012

Abstract

Background: Several studies assessed the relationship between the cholesterol ester transfer protein (CETP) Taq1B gene polymorphism (rs708272) with risk factors of cardiovascular diseases (CVDs). However, their findings were inconsistent. The present study investigated the relationship between CVD risk factors and the Taq1B variant in patients undergoing coronary angiography. 
Methods: This cross-sectional study was conducted on 476 patients aged 30-76 years old of both sexes from 2020-2021, in Yazd (Iran). The Taq1B polymorphism genotypes were evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on DNA extracted from whole blood. Standard protocols were used to measure cardio-metabolic markers. To determine the association between CVDs risk factors and the rs708272 variant, binary logistic regression was used in crude and adjusted models.
Results: Taq1B polymorphism genotype frequencies were 10.7% for B1B1, 72.3% for B1B2, and 17% for B2B2. There was no significant association between abnormal levels of CVDs risk factors and different genotypes of the Taq1B variant, Gensini score (P=0.64), Syntax score (P=0.79), systolic blood pressure (P=0.55), diastolic blood pressure (P=0.58), and waist circumference (P=0.79). There was no significant association between genotypes of the rs708272 variant and any abnormal serum lipid levels. After adjusting for confounders, the results remained non-significant.
Conclusion: There was no significant association between CVDs risk factors and CETP rs708272 polymorphism. The relationship between CETP gene variants and CVD occurrences varied across groups, implying that more research in different regions is required. 
A preprint version of this manuscript is available at https://www.researchsquare.com/article/rs-2575215/v1 with doi: 10.21203/rs.3.rs-2575215/v1.

Keywords

  1. Sahin B, Ilgun G. Risk factors of deaths related to cardiovascular diseases in World Health Organization (WHO) member countries. Health Soc Care Community. 2022;30:73-80. doi: 10.1111/hsc.13156. PubMed PMID: 32909378.
  2. Knopp RH. Risk factors for coronary artery disease in women. Am J Cardiol. 2002;89:28. doi: 10.1016/s0002-9149(02)02409-8. PubMed PMID: 12084401.
  3. Forman D, Bulwer BE. Cardiovascular disease: optimal approaches to risk factor modification of diet and lifestyle. Curr Treat Options Cardiovasc Med. 2006;8:47-57. doi: 10.1007/s11936-006-0025-7. PubMed PMID: 16401383.
  4. Roeters van Lennep JE, Westerveld HT, Erkelens DW, van der Wall EE. Risk factors for coronary heart disease: implications of gender. Cardiovasc Res. 2002;53:538-49. doi: 10.1016/s0008-6363(01)00388-1. PubMed PMID: 11861024.
  5. Katta N, Loethen T, Lavie CJ, Alpert MA. Obesity and Coronary Heart Disease: Epidemiology, Pathology, and Coronary Artery Imaging. Curr Probl Cardiol. 2021;46:100655. doi: 10.1016/j.cpcardiol.2020.100655. PubMed PMID: 32843206.
  6. Zhang YB, Pan XF, Chen J, Cao A, Xia L, Zhang Y, et al. Combined lifestyle factors, all-cause mortality and cardiovascular disease: a systematic review and meta-analysis of prospective cohort studies. J Epidemiol Community Health. 2021;75:92-9. doi: 10.1136/jech-2020-214050. PubMed PMID: 32892156.
  7. Guo SX, Yao MH, Ding YS, Zhang JY, Yan YZ, Liu JM, et al. Associations of Cholesteryl Ester Transfer Protein TaqIB Polymorphism with the Composite Ischemic Cardiovascular Disease Risk and HDL-C Concentrations: A Meta-Analysis. Int J Environ Res Public Health. 2016;13. doi: 10.3390/ijerph13090882. PubMed PMID: 27608031; PubMed Central PMCID: PMCPMC5036715.
  8. Mirmiran P, Esfandiar Z, Hosseini-Esfahani F, Koochakpoor G, Daneshpour MS, Sedaghati-Khayat B, et al. Genetic variations of cholesteryl ester transfer protein and diet interactions in relation to lipid profiles and coronary heart disease: a systematic review. Nutr Metab (Lond). 2017;14:77. doi: 10.1186/s12986-017-0231-1. PubMed PMID: 29234452; PubMed Central PMCID: PMCPMC5721696.
  9. Drayna D, Lawn R. Multiple RFLPs at the human cholesteryl ester transfer protein (CETP) locus. Nucleic Acids Res. 1987;15:4698. doi: 10.1093/nar/15.11.4698. PubMed PMID: 2884631; PubMed Central PMCID: PMCPMC340900.
  10. Boekholdt SM, Sacks FM, Jukema JW, Shepherd J, Freeman DJ, McMahon AD, et al. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation. 2005;111:278-87. doi: 10.1161/01.CIR.0000153341.46271.40. PubMed PMID: 15655129.
  11. Raina JK, Sharma M, Panjaliya RK, Dogra V, Bakaya A, Kumar P. Association of ESR1 (rs2234693 and rs9340799), CETP (rs708272), MTHFR (rs1801133 and rs2274976) and MS (rs185087) polymorphisms with Coronary Artery Disease (CAD). BMC Cardiovasc Disord. 2020;20:340. doi: 10.1186/s12872-020-01618-7. PubMed PMID: 32682401; PubMed Central PMCID: PMCPMC7368753.
  12. Rayat S, Ramezanidoraki N, Kazemi N, Modarressi MH, Falah M, Zardadi S, et al. Association study between polymorphisms in MIA3, SELE, SMAD3 and CETP genes and coronary artery disease in an Iranian population. BMC Cardiovasc Disord. 2022;22:298. doi: 10.1186/s12872-022-02695-6. PubMed PMID: 35768776; PubMed Central PMCID: PMCPMC9245199.
  13. Rahimi Z, Nourozi-Rad R, Vaisi-Raygani A, Saidi MR, Rahimi Z, Ahmadi R, et al. Association between cholesteryl ester transfer protein TaqIB variants and risk of coronary artery disease and diabetes mellitus in the population of western Iran. Genet Test Mol Biomarkers. 2011;15:813-9. doi: 10.1089/gtmb.2011.0037. PubMed PMID: 21689002.
  14. Elsammak MY, Al-Sharkaweey RM, Fahmy M, Reda AA, Farid W, Emara A, et al. Taq1B polymorphism of cholesteryl ester transfer protein (CETP) in Egyptian patients with metabolic syndrome. Diabetes Metab Syndr. 2011;5:61-5. doi: 10.1016/j.dsx.2010.12.009. PubMed PMID: 22813404.
  15. Jeenduang N, Porntadavity S, Nuinoon M, Horpet D, Thepkwan N, Thaworn P, et al. Studies of the CETP TaqIB and ApoE Polymorphisms in Southern Thai Subjects with the Metabolic Syndrome. Biochem Genet. 2015;53:184-99. doi: 10.1007/s10528-015-9680-2. PubMed PMID: 26014924.
  16. Hou H, Ma R, Guo H, He J, Hu Y, Mu L, et al. Association between Six CETP Polymorphisms and Metabolic Syndrome in Uyghur Adults from Xinjiang, China. Int J Environ Res Public Health. 2017;14. doi: 10.3390/ijerph14060653. PubMed PMID: 28629169; PubMed Central PMCID: PMCPMC5486339.
  17. Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-97. doi: 10.1001/jama.285.19.2486. PubMed PMID: 11368702.
  18. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15:539-53. doi: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S. PubMed PMID: 9686693.
  19. Moghaddam MB, Aghdam FB, Jafarabadi MA, Allahverdipour H, Nikookheslat SD, Safarpour S. The Iranian Version of International Physical Activity Questionnaire (IPAQ) in Iran: content and construct validity, factor structure, internal consistency and stability. World Appl Sci J. 2012;18:1073-80.
  20. Avci A, Fidan S, Tabakci MM, Toprak C, Alizade E, Acar E, et al. Association between the Gensini Score and Carotid Artery Stenosis. Korean Circ J. 2016;46:639-45. doi: 10.4070/kcj.2016.46.5.639. PubMed PMID: 27721854; PubMed Central PMCID: PMCPMC5054175.
  21. Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol. 1983;51:606. doi: 10.1016/s0002-9149(83)80105-2. PubMed PMID: 6823874.
  22. Ipek E, Ermis E, Uysal H, Kizilet H, Demirelli S, Yildirim E, et al. The relationship of micronucleus frequency and nuclear division index with coronary artery disease SYNTAX and Gensini scores. Anatol J Cardiol. 2017;17:483-9. doi: 10.14744/AnatolJCardiol.2017.7582. PubMed PMID: 28315571; PubMed Central PMCID: PMCPMC5477082.
  23. Guidelines for percutaneous transluminal coronary angioplasty. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). J Am Coll Cardiol. 1988;12:529-45. PubMed PMID: 2969021.
  24. Ramezani-Jolfaie N, Aghaei S, Farashahi Yazd E, Moradi A, Mozaffari-Khosravi H, Amiri M, et al. The combined effects of cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism and canola, sesame and sesame-canola oils consumption on metabolic response in patients with diabetes and healthy people. J Cardiovasc Thorac Res. 2020;12:185-94. doi: 10.34172/jcvtr.2020.32. PubMed PMID: 33123324; PubMed Central PMCID: PMCPMC7581849.
  25. Lu Y, Tayebi N, Li H, Saha N, Yang H, Heng CK. Association of CETP Taq1B and -629C > A polymorphisms with coronary artery disease and lipid levels in the multi-ethnic Singaporean population. Lipids Health Dis. 2013;12:85. doi: 10.1186/1476-511X-12-85. PubMed PMID: 23758630; PubMed Central PMCID: PMCPMC3699414.
  26. Kashani Farid MA, Azizi F, Hedayati M, Daneshpour MS, Shamshiri AR, Siassi F. Association between CETP Taq1B and LIPC -514C/T polymorphisms with the serum lipid levels in a group of Tehran’s population: a cross sectional study. Lipids Health Dis. 2010;9:96. doi: 10.1186/1476-511X-9-96. PubMed PMID: 20822508; PubMed Central PMCID: PMCPMC2944238.
  27. Daneshpour M, Hedayati M, Azizi F. TaqI B1/B2 and -629A/C cholesteryl ester transfer protein (CETP) gene polymorphisms and their association with CETP activity and high-density lipoprotein cholesterol levels in a Tehranian population. Part of the Tehran Lipid and Glucose Study (TLGS). Genetics and Molecular Biology. 2007;30:1039-46. doi: 1590/s1415-47572007000600001.
  28. Abd El-Aziz TA, Mohamed RH, Hagrass HA. Increased risk of premature coronary artery disease in Egyptians with ABCA1 (R219K), CETP (TaqIB), and LCAT (4886C/T) genes polymorphism. J Clin Lipidol. 2014;8:381-9. doi: 10.1016/j.jacl.2014.06.001. PubMed PMID: 25110219.
  29. Kaman D, Ilhan N, Ilhan N, Akbulut M. TaqIB and severity of coronary artery disease in the Turkish population: a pilot study. Bosn J Basic Med Sci. 2015;15:9-13. doi: 10.17305/bjbms.2015.157. PubMed PMID: 25725138; PubMed Central PMCID: PMCPMC4365681.
  30. Wang J, Wang LJ, Zhong Y, Gu P, Shao JQ, Jiang SS, et al. CETP gene polymorphisms and risk of coronary atherosclerosis in a Chinese population. Lipids Health Dis. 2013;12:176. doi: 10.1186/1476-511X-12-176. PubMed PMID: 24283500; PubMed Central PMCID: PMCPMC4220746.
  31. Iwanicka J, Iwanicki T, Niemiec P, Balcerzyk A, Krauze J, Gorczynska-Kosiorz S, et al. Relationship between CETP gene polymorphisms with coronary artery disease in Polish population. Mol Biol Rep. 2018;45:1929-35. doi: 10.1007/s11033-018-4342-1. PubMed PMID: 30178218; PubMed Central PMCID: PMCPMC6267260.
  32. Corella D, Carrasco P, Fito M, Martinez-Gonzalez MA, Salas-Salvado J, Aros F, et al. Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population. J Lipid Res. 2010;51:2798-807. doi: 10.1194/jlr.P005199. PubMed PMID: 20581105; PubMed Central PMCID: PMCPMC2918462.
  33. Porchay-Balderelli I, Pean F, Bellili N, Jaziri R, Marre M, Fumeron F, et al. The CETP TaqIB polymorphism is associated with the risk of sudden death in type 2 diabetic patients. Diabetes Care. 2007;30:2863-7. doi: 10.2337/dc07-0869. PubMed PMID: 17666459.
  34. El-Lebedy D. Interaction between endothelial nitric oxide synthase rs1799983, cholesteryl ester-transfer protein rs708272 and angiopoietin-like protein 8 rs2278426 gene variants highly elevates the risk of type 2 diabetes mellitus and cardiovascular disease. Cardiovasc Diabetol. 2018;17:97. doi: 10.1186/s12933-018-0742-8. PubMed PMID: 29973202; PubMed Central PMCID: PMCPMC6032560.
  35. Lopez-Rios L, Novoa FJ, Chirino R, Varillas F, Boronat-Cortes M, Wagner AM. Interaction between cholesteryl ester transfer protein and hepatic lipase encoding genes and the risk of type 2 diabetes: results from the Telde study. PLoS One. 2011;6:e27208. doi: 10.1371/journal.pone.0027208. PubMed PMID: 22073289; PubMed Central PMCID: PMCPMC3207838.
  36. Perez-Robles M, Campos-Perez W, Torres-Vanegas J, Rodriguez-Reyes SC, Rivera-Valdes JJ, Martinez-Lopez E. Abdominal obesity, excessive adiposity and Taq1B CETP variant are positively associated with serum lipids in Mexican women. Lifestyle Genom. 2023. doi: 10.1159/000529053. PubMed PMID: 36652934.
  37. Vohl MC, Lamarche B, Pascot A, Leroux G, Prud’homme D, Bouchard C, et al. Contribution of the cholesteryl ester transfer protein gene TaqIB polymorphism to the reduced plasma HDL-cholesterol levels found in abdominal obese men with the features of the insulin resistance syndrome. Int J Obes Relat Metab Disord. 1999;23:918-25. doi: 10.1038/sj.ijo.0800972. PubMed PMID: 10490796.
  38. Campos-Perez W, Perez-Robles M, Torres-Castillo N, Rodriguez-Reyes SC, De la Cerda Trujillo LF, Navarro-Muniz E, et al. Physical inactivity and excessive sucrose consumption are associated with higher serum lipids in subjects with Taq1B CETP polymorphism. J Hum Nutr Diet. 2020;33:299-307. doi: 10.1111/jhn.12747. PubMed PMID: 32163222.
  39. Paromov VM, Morton RE. Lipid transfer inhibitor protein defines the participation of high density lipoprotein subfractions in lipid transfer reactions mediated by cholesterol ester transfer protein (CETP). J Biol Chem. 2003;278:40859-66. doi: 10.1074/jbc.M306580200. PubMed PMID: 12907677.