Effect of ABCA1-R219K Polymorphism in Serum Lipid Parameters in Patients under Statin Therapy Visiting Tertiary Cardiac Center of Nepal

Abstract

Introduction ATP-binding cassette transporter A1 (ABCA1) encoded by ABCA1 gene is one of the important protein involved in lipid metabolism. The effect of statin therapy on dyslipidemia varies among individuals and it may be due to different genetic polymorphism. The R219K polymorphism of ABCA1 gene is found to have a significant role in the response of statin.

Objective This study was designed to evaluate the effect of R219K polymorphism in lipid-lowering action of statin in patients with dyslipidemia.

Material and Methods This study was conducted in 88 patients. Blood samples were taken from patients before and at the end of 3 months of statin use and were analyzed for lipid profile. Whole blood was analyzed for R219K Polymorphism using polymerase chain reaction-restriction fragment length polymorphism.

Results R219K polymorphism was associated with significant percentage reduction of serum triglyceride/high-density lipoprotein (TG/HDL) ratio and total cholesterol/high-density lipoprotein (TC/HDL) ratio in atorvastatin users. However, there was no significant association of polymorphism with change in serum TC, HDL-C, LDL-C, TG, and very low-density lipoprotein (VLDL). Among KK genotype individuals, value of TG, VLDL, TG/HDL, and TC/HDL were significantly lower than in RR genotypes. Also, TG/HDL and TC/HDL were significantly lower in RK genotype than in RR. Treatment of dyslipidemia with statin was found to be comparatively better in patients having the genotypes KK and RK.

Conclusion Our study demonstrated association of R219K polymorphism with the significant reduction of TG/HDL and TC/HDL and particularly the KK genotype was associated with significant improvement of lipid parameters following atorvastatin treatment.

Keywords

R219K polymorphism - PCR-RFLP - lipid profile - single-nucleotide polymorphisms - dyslipidemia - atorvastatin - statin therapy

Data Availability

All the data used and/or analyzed in this study can make available from the corresponding author on request.

Patient Consent

The informed consent was obtained from all the individual patients.

Ethical Approval

This study was approved by the Institutional Review committee (IRC), Institute of Medicine (IOM), Kathmandu, Nepal (IRC reference number: 320(6–11-E) 2/074/075).

Consent for Publication

I, Binod Kumar Yadav, corresponding author of this manuscript give full consent for publication on behalf of all co-authors.

Authors' Contribution

S.G. performed laboratory work, statistical analysis, and manuscript writing. BKY helped in designing the study, analysis of the data, and writing of the manuscript and proof reading. J.S. contributed to laboratory work standardization, data analysis, and proof reading. S.S. and D.S. supported in laboratory work. V.K.S., E.T.T., M.R., and A.B. conceived the study and participated in the design and coordination of the study. K.D.M., C.M.P., and V.P. read and approved the final manuscript.

Publication History

Received: 22 September 2022

Accepted: 26 February 2023

Article published online:
03 July 2023

• References

• 1 Kang YJ, Wang HW, Cheon SY, Lee HJ, Hwang KM, Yoon HS. Associations of obesity and dyslipidemia with intake of sodium, fat, and sugar among Koreans: a qualitative systematic review. Clin Nutr Res 2016; 5 (04) 290-304
• 2 Lin C-F, Chang Y-H, Chien S-C, Lin Y-H. Yeh H-Y. Epidemiology of dyslipidemia in the Asia Pacific region. Int J Gerontol 2018; 12 (01) 2-6
• 3 Qi L, Ding X, Tang W. et al. Prevalence and risk factors associated with dyslipidemia in Chongqing, China. Int J Environ Res Public Health 2015; 12 (10) 13455-13465
• 4 Sukhorukov V, Karagodin V, Orekhov AN. Modern methods of diagnosis dyslipidemia. Patol Fiziol Eksp Ter 2016; 60 (01) 65-72
• 5 Parhofer KJDI. Update dyslipidemia. 2013;54(9):1089–103
• 6 Jacobson TA, Ito MK, Maki KC. et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1—full report. J Clin Lipidol 2015; 9 (02) 129-169
• 7 Bonfim MR, Oliveira ASB, Amaral SLd, Monteiro HL. Treatment of dyslipidemia with statins and physical exercises: recent findings of skeletal muscle responses. Arq Bras Cardiol 2015; 104: 324-331
• 8 Clark LT. Treating dyslipidemia with statins: the risk-benefit profile. Am Heart J 2003; 145 (03) 387-396
• 9 Ramkumar S, Raghunath A, Raghunath S. Statin therapy: review of safety and potential side effects. Acta Cardiol Sin 2016; 32 (06) 631
• 10 Mandal CC. High cholesterol deteriorates bone health: new insights into molecular mechanisms. Front Endocrinol (Lausanne) 2015; 6: 165
• 11 Jones PH, McKenney JM, Karalis DG, Downey J, Journal NIJAH. Comparison of the efficacy and safety of atorvastatin initiated at different starting doses in patients with dyslipidemia. Am Heart J 2005; 149 (01) e1-e8
• 12 Bhattarai AK, Acharya A, Karki PK. Use of statins as lipid lowering agent in hypercholesterolemia in a tertiary care hospital: a descriptive cross-sectional study. J Nepal Med Assoc 2020; 58 (232) 1031-1035
• 13 Kansu B, Lang D. . Genetic polymorphisms as predictive markers for statin therapy: a route to improved cardiovascular patient outcomes? JBHTIJoSR 2017;10
• 14 Ergen A, Isbir S, Tekeli A, Isbir T. Investigation of ABCA1 C69T and G-191C polymorphisms in coronary artery disease. In Vivo 2008; 22 (02) 187-90
• 15 Guo Z, Wu P, Xie D, Wang Q, Liu Y, Cha Z. et al. A new discovered ABCA1 gene polymorphisms and the association of ABCA1 SNPs with coronary artery disease and plasma lipids in Chinese population. 2011 ;26(4):179–90
• 16 Ghaznavi H, Aali E, Soltanpour MS. Association study of the ATP-binding cassette transporter A1 (ABCA1) Rs2230806 genetic variation with lipid profile and coronary artery disease risk in an Iranian population. Open Access Maced J Med Sci 2018; 6 (02) 274-279
• 17 Genvigir FDV, Soares SA, Hirata MH. et al. Effects of ABCA1 SNPs, including the C-105T novel variant, on serum lipids of Brazilian individuals. Chin Chim Acta 2008; 389 (1–2): 79-86
• 18 Lutucuta S, Ballantyne CM, Elghannam H, Gotto Jr AM, Marian AJ. Novel polymorphisms in promoter region of ATP binding cassette transporter gene and plasma lipids, severity, progression, and regression of coronary atherosclerosis and response to therapy. Circ Res 2001; 88 (09) 969-73
• 19 Ceccanti M, Cambieri C, Frasca V, Onesti E, Biasiotta A, Giordano C. et al. A novel mutation in ABCA1 gene causing Tangier disease in an Italian family with uncommon neurological presentation. Front Neurol 2016; 7: 185
• 20 Saleheen D, Khanum S, Haider SR, Nazir A, Ahmad U, Khalid H. et al. A novel haplotype in ABCA1 gene effects plasma HDL-C concentration. Int J Cardiol 2007; 115 (01) 7-13
• 21 Wang N, Silver DL, Thiele C, Tall AR. ATP-binding cassette transporter A1 (ABCA1) functions as a cholesterol efflux regulatory protein. J Biol Chem 2001; 276 (26) 23742-7
• 22 Zargar S, Wakil S, Mobeirek AF, Al-Jafari AA. Involvement of ATP-binding cassette, subfamily A polymorphism with susceptibility to coronary artery disease. Biomed Rep 2013; 1 (06) 883-8
• 23 Wu Y, Bai H, Liu R, Liu Y, Liu B. Analysis of ATP binding cassette A1 gene R219K polymorphism in patients with endogenous hypertriglyceridemia in Chinese population. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2007; 24 (02) 177-181
• 24 Pontoriero AC, Trinks J, Hulaniuk ML, Caputo M, Fortuny L, Pratx LB. et al. Influence of ethnicity on the distribution of genetic polymorphisms associated with risk of chronic liver disease in South American populations. 2015;16(1):1–8
• 25 May S. Rapid Extraction of High Quality DNA from Whole Blood Stored at 4°C for Long Period
• 26 Kolovou V, Marvaki A, Boutsikou M, Vasilopoulos G, Degiannis D, Marvaki C. et al. Effect of ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms on plasma lipid variables and common demographic parameters in Greek nurses. 2016 ;10:233
• 27 Pradeepa R, Mohan V. Epidemiology of Dyslipidemia in India. 2017
• 28 Kopin L. Lowenstein CJJAoim. Dyslipidemia. 2017; 167 (11) ITC81-ITC96
• 29 Sorace P, LaFontaine T, Thomas TR. Know the risks: lifestyle management of dyslipidemia. ACSM's Health Fit J 2006; 10 (04) 18-25
• 30 Zineh I. Pharmacogenetics of response to statins. Curr Atheroscler Rep 2007; 9 (03) 187-194
• 31 Clee SM, Zwinderman AH, Engert JC. et al. Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease. Circulation 2001; 103 (09) 1198-1205
• 32 Mantaring M, Rhyne J, Hong SH, Miller M. Genotypic variation in ATP-binding cassette transporter-1 (ABCA1) as contributors to the high and low high-density lipoprotein-cholesterol (HDL-C) phenotype. Transl Res 2007; 149 (04) 205-210
• 33 Akao H, Polisecki E, Schaefer EJ. et al. ABCA1 gene variation and heart disease risk reduction in the elderly during pravastatin treatment. Atherosclerosis 2014; 235 (01) 176-181
• 34 Li J, Wang LF, Li ZQ, Pan W. Effect of R219K polymorphism of the ABCA1 gene on the lipid-lowering effect of pravastatin in Chinese patients with coronary heart disease. Clin Exp Pharmacol Physiol 2009; 36 (5-6): 567-570
• 35 Mokuno J, Hishida A, Morita E. et al. ATP-binding cassette transporter A1 (ABCA1) R219K (G1051A, rs2230806) polymorphism and serum high-density lipoprotein cholesterol levels in a large Japanese population: cross-sectional data from the Daiko Study. Endocr J 2015; •••: EJ14-EJ0577
• 36 Maruyama C, Imamura K, Teramoto T. Assessment of LDL particle size by triglyceride/HDL-cholesterol ratio in non-diabetic, healthy subjects without prominent hyperlipidemia. J Atheroscler Thromb 2003; 10 (03) 186-191