Document Type : Short Communication
- Mohammad Javad Ghorbani 1
- Nematollah Razmi 2
- Seyed Mohammad Bagher Tabei 3
- Mohammad Javad Zibaeenezhad 4
- Hamid Reza Goodarzi 5
1 PhD Candidate, Department of Genetics, Fars Science and Research Branch AND Marvdasht Branch, Islamic Azad University, Marvdasht, Iran
2 Associate Professor, Department of Biochemistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran
3 Associate Professor, Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
4 Professor, Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
5 Assistant Professor, Department of Genetics, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran
BACKGROUND: Myocardial infarction (MI) is a multifactorial disease caused by the suspension of blood circulation in a part of the myocardium. Understanding the genetic basis of MI can provide insight regarding the pathogenesis of the disease. The aim of this study was to investigate the association between pathogenic mutations and early-onset MI in five families with familial MI and without common MI risk factor.METHODS: Patients with MI younger than 50 years with family history of MI and without common diagnostic criteria (obesity, diabetes, familial hypercholesterolemia, opium/alcohol use) were evaluated for pathogenic mutations by whole exome sequencing (WES) and mutation was confirmed by polymerase chain reaction (PCR)-Sanger sequencing.RESULTS: The c.2855G > A missense mutation with homozygous autosomal recessive inheritance was identified in low-density lipoprotein receptor-related protein 8 (LRP8) gene in all patients of a family.CONCLUSION: The c.2855G > A (R952Q) mutation in LRP8 gene in homozygous state could be considered as a possible etiology of early-onset familial MI.
- Shanmugam K, Ravindran S, Kurian GA, Rajesh M. Fisetin confers cardioprotection against myocardial ischemia reperfusion injury by suppressing mitochondrial oxidative stress and mitochondrial dysfunction and inhibiting glycogen synthase kinase 3beta Activity. Oxid Med Cell Longev 2018; 2018: 9173436.
- Biglu MH, Ghavami M, Biglu S. Cardiovascular diseases in the mirror of science. J Cardiovasc Thorac Res 2016; 8(4): 158-63.
- Asif M, Bhat S, Nizamuddin S, Mustak MS. TG haplotype in the LRP8 is associated with myocardial infarction in south Indian population. Gene 2018; 642: 225-9.
- InanlooRahatloo K, Parsa AF, Huse K, Rasooli P, Davaran S, Platzer M, et al. Mutation in ST6GALNAC5 identified in family with coronary artery disease. Sci Rep 2014; 4: 3595.
- Chen QF, Wang W, Huang Z, Huang DL, Li T, Wang F, et al. Correlation of rs1122608 SNP with acute myocardial infarction susceptibility and clinical characteristics in a Chinese Han population: A case-control study. Anatol J Cardiol 2018; 19(4): 249-58.
- Kelloniemi A, Szabo Z, Serpi R, Napankangas J, Ohukainen P, Tenhunen O, et al. The Early-Onset Myocardial Infarction Associated PHACTR1 Gene Regulates Skeletal and Cardiac Alpha-Actin Gene Expression. PLoS One 2015; 10(6): e0130502.
- Dai X, Wiernek S, Evans JP, Runge MS. Genetics of coronary artery disease and myocardial infarction. World J Cardiol 2016; 8(1): 1-23.
- Stacey RB, Leaverton PE, Schocken DD, Peregoy JA, Bertoni AG. Prediabetes and the association with unrecognized myocardial infarction in the multi-ethnic study of atherosclerosis. Am Heart J 2015; 170(5): 923-8.
- Seidelmann SB, Smith E, Subrahmanyan L, Dykas D, Abou Ziki MD, Azari B, et al. Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults. Circ Cardiovasc Genet 2017; 10(1).
- Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012; 60(16): 1581-98.
- 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) final report. Circulation 2002; 106(25): 3143-421.
- Mohseni J, Kazemi T, Maleki MH, Beydokhti H. A systematic review on the prevalence of acute myocardial infarction in Iran. Heart Views 2017; 18(4): 125-32.
- Gao Y, Lee C, Song J, Li S, Cui Y, Liu Y, et al. Digenic mutations on SCAP and AGXT2 predispose to premature myocardial infarction. Oncotarget 2017; 8(59): 100141-9.
- Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 2017; 135(10): e146-e603.
- Do R, Stitziel NO, Won HH, Jorgensen AB, Duga
- S, Angelica Merlini P, et al. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature 2015; 518(7537): 102-6.
- Shen GQ, Li L, Wang QK. Genetic variant R952Q in LRP8 is associated with increased plasma triglyceride levels in patients with early-onset CAD and MI. Ann Hum Genet 2012; 76(3): 193-9.
- Martinelli N, Olivieri O, Shen GQ, Trabetti E, Pizzolo F, Busti F, et al. Additive effect of LRP8/APOER2 R952Q variant to APOE epsilon2/epsilon3/epsilon4 genotype in modulating apolipoprotein E concentration and the risk of myocardial infarction: a case-control study. BMC Med Genet 2009; 10: 41.
- Shen GQ, Li L, Girelli D, Seidelmann SB, Rao S, Fan C, et al. An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction. Am J Hum Genet 2007; 81(4): 780-91.
- Hirai H, Yasui N, Yamashita K, Tabata S, Yamamoto M, Takagi J, et al. Structural basis for ligand capture and release by the endocytic receptor ApoER2. EMBO Rep 2017; 18(6): 982-99.
- Li M, Huang L, Grigoroiu-Serbanescu M, Bergen SE, Landen M, Hultman CM, et al. Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis. Mol Neurobiol 2016; 53(10): 6608-19.
- Shen GQ, Girelli D, Li L, Rao S, Archacki S, Olivieri O, et al. A novel molecular diagnostic marker for familial and early-onset coronary artery disease and myocardial infarction in the LRP8 gene. Circ Cardiovasc Genet 2014; 7(4): 514-20.