Document Type : Original Article(s)
- Mahsa Rahimi 1
- Hossein Khanahmad 1
- Mojgan Gharipour 2
- Hamidreza Roohafza 3
- Minoo Dianatkhah 4
- Elham Khosravi 5
- Ladan Sadeghian 2
- Masoumeh Sadeghi 6
1 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Genetics and Epigenetics, Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
3 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
4 Heart Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
5 Interventional Cardiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
6 Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
BACKGROUND: Myocardial infarction (MI) is one of the leading causes of mortality globally. Although it is most prevalent in the elderly, it may occur in young adults (men ≤ 55 years or women ≤ 65 years) as premature MI (PMI). As awareness of genetic risks may lead to effective prevention of PMI, we aim to investigate the association of two susceptible single nucleotide polymorphisms (SNPs) in the LPA gene with PMI in the Iranian population, rs1801693 and rs7765781, identified in previous genome-wide association studies (GWAS).METHODS: A total number of 85 patients with PMI and 85 healthy controls were recruited from December 2015 to March 2016 from Isfahan, Iran. Peripheral blood samples were collected from all individuals. Deoxyribonucleic acid (DNA) was extracted and genotyped at rs1181693 and rs7765781 polymorphisms, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results were statistically analyzed to find any possible association of the two polymorphisms with PMI by SPSS software and P-values less than 0.05 were considered to be statistically significant.RESULTS: Statistical analysis displayed no significant difference between rs1801693 (P = 0.815)/rs7765781 (P = 0.746) alleles in patients with PMI and healthy control subjects.CONCLUSION: There is no meaningful association between rs1801693/rs7765781 and PMI incidence in the Iranian population.
- World Health Organization. Noncommunicable diseases country profiles 2018 [Online]. [cited 2020 Oct 2]. Available from: URL: http://www.who.int/nmh/publications/ncd-profiles-2018/en/
- Mechanic OJ, Gavin M, Grossman SA. Acute Myocardial Infarction. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021.
- Dugani SB, Murad W, Damilig K, Atos J, Mohamed E, Callachan E, et al. Premature Myocardial Infarction in the Middle East and North Africa: Rationale for the Gulf PREVENT Study. Angiology 2019; 71(1): 17-26.
- Pineda J, Marin F, Roldan V, Valencia J, Marco P, Sogorb F. Premature myocardial infarction: Clinical profile and angiographic findings. Int J Cardiol 2008; 126(1): 127-9.
- Hbejan K. Smoking effect on ischemic heart disease in young patients. Heart Views 2011; 12(1): 1-6.
- Kazemi T, Sharifzadeh GR, Zarban A, Fesharakinia A, Rezvani MR, Moezy SA. Risk factors for premature myocardial infarction: A matched case-control study. J Res Health Sci 2011; 11(2): 77-82.
- Ranthe MF, Petersen JA, Bundgaard H, Wohlfahrt J, Melbye M, Boyd HA. A detailed family history of myocardial infarction and risk of myocardial infarction--a nationwide cohort study. PLoS One 2015; 10(5): e0125896.
- Shah N, Kelly AM, Cox N, Wong C, Soon K. Myocardial infarction in the "Young": Risk factors, presentation, management and prognosis. Heart Lung Circ 2016; 25(10): 955-60.
- Dehghan A, Bis JC, White CC, Smith AV, Morrison AC, Cupples LA, et al. Genome-wide association study for incident myocardial infarction and coronary heart disease in prospective cohort studies: The CHARGE Consortium. PLoS One 2016; 11(3): e0144997.
- Kathiresan S, Voight BF, Purcell S, Musunuru K, Ardissino D, Mannucci PM, et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet 2009; 41(3): 334-41.
- Peden JF, Hopewell JC, Saleheen D, Chambers JC, Hager J, Soranzo N, et al. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat Genet 2011; 43(4): 339-44.
- Schunkert H, Konig IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet 2011; 43(4): 333-8.
- Tregouet DA, Konig IR, Erdmann J, Munteanu A, Braund PS, Hall AS, et al. Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nat Genet 2009; 41(3): 283-5.
- Cai G, Huang Z, Zhang B, Yu L, Li L. Elevated lipoprotein (a) levels are associated with the acute myocardial infarction in patients with normal low-density lipoprotein cholesterol levels. Biosci Rep 2019; 39(4).
- Song ZK, Wu HD, Cao HY, Qin L. The association between the LPA gene polymorphism and coronary artery disease in Chinese Han population. Biomed Res Int 2014; 2014: 370670.
- Song ZK, Cao HY, Wu HD, Zhou LT, Qin L. LPA Gene polymorphisms and gene expression associated with coronary artery disease. Biomed Res Int 2017; 2017: 4138376.
- Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 2009; 301(22): 2331-9.
- Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 2009; 302(4): 412-23.
- Enas EA, Varkey B, Dharmarajan TS, Pare G, Bahl VK. Lipoprotein(a): An independent, genetic, and causal factor for cardiovascular disease and acute myocardial infarction. Indian Heart J 2019; 71(2): 99-112.
- Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 2009; 361(26): 2518-28.
- Koch W, Mueller JC, Schrempf M, Wolferstetter H, Kirchhofer J, Schomig A, et al. Two rare variants explain association with acute myocardial infarction in an extended genomic region including the apolipoprotein(A) gene. Ann Hum Genet 2013; 77(1): 47-55.
- Suguna S, Nandal DH, Kamble S, Bharatha A, Kunkulol R. Genomic DNA isolation from human whole blood samples by non enzymatic salting out method. Int J Pharm Pharm Sci 2014; 6(6): 198-9.
- Dugani SB, Ayala Melendez AP, Reka R, Hydoub YM, McCafferty SN, Murad MH, et al. Risk factors associated with premature myocardial infarction: A systematic review protocol. BMJ Open 2019; 9(2): e023647.
- Kazemi T, Sharifzadeh G, Zarban A, Fesharakinia A. Comparison of components of metabolic syndrome in premature myocardial infarction in an Iranian population: A case -control study. Int J Prev Med 2013; 4(1): 110-4.
- Zera E, Zaimi E, Metalla M, Prifti S, Zera E. Diabetes mellitus, the important cardiovascular risk factor of premature myocardial infarction in women. Heart 2012; 98(Suppl 2): E108-E109.
- Xu S, Cheng J, Li NH, Chen YN, Cai MY, Tang SS, et al. The association of APOC4 polymorphisms with premature coronary artery disease in a Chinese Han population. Lipids Health Dis 2015; 14: 63.
- Dong C, Fu Z, Wang B, Zhu Q, Cha E, Huang D, et al. GW26-e2181 association of LPA genetic polymorphisms with coronary artery disease in the Xinjiang Han and Uygur population of China. J Am Coll Cardiol 2015; 66(16_Suppl): C53.
- Rouhani B, Ghaderian SMH, Salehi Z. Investigation of LPA sequence variants rs6415084, rs3798220 with conventional coronary artery disease in Iranian CAD patients. Hum Antibodies 2019; 27(2): 99-104.
- Mirhafez SR, Avan A, Khatamianfar S, Ghasemi F, Moohebati M, Ebrahimi M, et al. There is an association between a genetic polymorphism in the ZNF259 gene involved in lipid metabolism and coronary artery disease. Gene 2019; 704: 80-5.
- Ahani M, Ghaderin SMH, Azargashb E, Hasanzad M. Lack of association between Rs10755578 polymorphisms of lipoprotein(A) gene and coronary artery disease in Iranian population. Acta Medica Mediterranea, 2015, 31: 907.
- Dai W, Long J, Cheng Y, Chen Y, Zhao S. Elevated plasma lipoprotein(a) levels were associated with increased risk of cardiovascular events in Chinese patients with stable coronary artery disease. Sci Rep 2018; 8(1): 7726.
- Azarfarin R, Dashti M, Totonchi Z, Ziyaeifard M, Mehrabanian M, Gorjipour F, et al. High serum lipoprotein (a) as an independent risk factor for premature coronary artery disease in the Iranian population. Iranian Heart Journal 2017; 18(2): 17-22.
- Kazemi T, Sharifzadeh Ghr, Zarban A, Fesharakinia Azit. Lipoprotein (A) in patients with premature myocardial infarction. ARYA Atheroscler 2009; 4(4): 149-51.
- Mirzaei M, Rahnama A, Esmaeiliyan F, Bakhshi H. Serum level of lipoprotein a (LPa) in patients with premature myocardial infarction. J Rafsanjan Univ Med Sci 2013; 12(8): 655-66. [In Persian].
- Yousefi AA, Givtaj N, Zavareh A, Sabourizadeh N, Chizaree MR. Lipoprotein A (Lpa), fibrinogen and homocysteine in patients with coronary artery disease and without major risk factors. Iranian Heart Journal 2006; 7(1): 36-9.
- Rezvan H, Rahimi F, Darvish H. Lipoprotein (A)
- levels and coronary artery disease in Iranian patients. Is there a link? Acta Med Iran 2004; 4: 263-6.
- Khera AV, Everett BM, Caulfield MP, Hantash FM, Wohlgemuth J, Ridker PM, et al. Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk. Circulation 2014; 129(6): 635-42.
- Nestel PJ, Barnes EH, Tonkin AM, Simes J, Fournier M, White HD, et al. Plasma lipoprotein(a) concentration predicts future coronary and cardiovascular events in patients with stable coronary heart disease. Arterioscler Thromb Vasc Biol 2013; 33(12): 2902-8.
- Albers JJ, Slee A, O'Brien KD, Robinson JG, Kashyap ML, Kwiterovich PO, et al. Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes). J Am Coll Cardiol 2013; 62(17): 1575-9.
- Patel AP, Wang () M, Pirruccello JP, Ellinor PT, Ng K, Kathiresan S, et al. Lp(a) (Lipoprotein[a]) concentrations and incident atherosclerotic cardiovascular disease: new insights from a large national Biobank. Arterioscler Thromb Vasc Biol 2021; 41(1): 465-74.
- Guddeti RR, Patil S, Ahmed A, Sharma A, Aboeata A, Lavie CJ, et al. Lipoprotein(a) and calcific aortic valve stenosis: A systematic review. Prog Cardiovasc Dis 2020; 63(4): 496-502.
- Marcovina SM, Koschinsky ML. Evaluation of lipoprotein(a) as a prothrombotic factor: progress from bench to bedside. Curr Opin Lipidol 2003; 14(4): 361-6.
- Vavuranakis MA, Jones SR, Cardoso R, Gerstenblith G, Leucker TM. The role of Lipoprotein(a) in cardiovascular disease: Current concepts and future perspectives. Hellenic J Cardiol 2020; 61(6): 398-403.
- Dai X, Wiernek S, Evans JP, Runge MS. Genetics of coronary artery disease and myocardial infarction. World J Cardiol 2016; 8(1): 1-23.