Association of Polymorphisms at LDLR Locus with Coronary Artery Disease Independently from Lipid Profile
-
Seyed Hamid Jamaldini
,
Mojgan Babanejad
,
Reza Mozaffari
,
Nooshin Nikzat
,
Khadijeh Jalalvand
,
Azadeh Badiei
,
Hamidreza Sanati
,
Farshad Shakerian
,
Mahdi Afshari
,
Kimia Kahrizi
,
Hossein Najmabadi
Abstract
Coronary artery disease (CAD) is the leading cause of mortality in many parts of the world. Genome-wide association studies (GWAS) have identified several genetic variants associated with CAD in Low-density lipoprotein receptor (LDLR) locus. This study was evaluated the possible association of genetic markers at LDLR locus with CAD irrespective to lipid profile and as well as the association of these SNPs with severity of CAD in Iranian population. Sequencing of 2 exons in LDLR gene (Exon 2, 12) and part of intron 30 of SMARCA4 gene include rs1122608, was performed in 170 Iranian patients angiographically confirmed CAD and 104 healthy controls by direct sequencing. Sullivan's scoring system was used for determining the severity of CAD in cases. Our results showed that homozygote genotypes of rs1122608 (P<0.0001), rs4300767 (P<0.005) and rs10417578 (p<0.007) SNPs have strong protective effects on the CAD. In addition, we found that rs1122608 (GT or TT) was at higher risk of three vessel involvement compared to single vessels affecting (P=0.01).
KulloIJ, Ding K. Mechanisms of disease: the genetic basisof coronary heart disease. Nat Clin Pract Cardiovasc Med 2007;4(10):558-69.
World Health Organization. The World Health Report, 2002: reducing risks, promoting healthy life. Geneva, 2002.
Franchini M, Peyvandi F, Mannucci PM. The genetic basis of coronary artery disease: from candidate genes to whole genome analysis. Trends Cardiovasc Med 2008;18(5):157-62.
Padmanabhan S, Hastie C, Prabhakaran D. Genomic approaches to coronary artery disease. Indian J Med Res 2010;132(5):567-78.
Musunuru K, Kathiresan S. Genetics of Coronary Artery Disease. Annu Rev Genomics Hum Genet 2010;11(1):91-108.
Girelli D, Martinelli N, Peyvandi F. Genetic architecture of coronary artery disease in the genome-wide era: implications for the emerging ‘‘golden dozen’’ loci. SeminThrombHemost 2009;35(7):671-82.
Weissglas-Volkov D, Pajukanta P. Genetic causes of high and low serum HDL-cholesterol. J Lipid Res 2010;51(8):2032-57.
Fishbein MC. The vulnerable and unstable atherosclerotic plaque. Cardiovasc Pathol 2010;19(1):6-11.
Bui QT, Prempeh M, Wilensky RL. Atherosclerotic plaque development. Int J Biochem Cell Biol 2009;41(11):2109-13.
Samani NJ, Erdmann J, Hall AS, et al. Genome wide association analysis of coronary artery disease. N Engl J Med 2007;357(5):443-53.
Roberts R, Stewart AF. Genes and coronary artery disease: where are we? J Am Coll Cardiol 2012;60(18):1715-21.
Kathiresan S, Willer CJ, Peloso GM, et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 2009;41(1):56-65.
Kathiresan S, Voight BF, Purcell S, 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.
Linsel-Nitschke P, Götz A, Erdmann J, et al. Lifelong reduction of LDL-Crelated to a common variant in theLDL-receptor gene decreases the risk of coronary artery disease: a MendelianRandomisation study. PLoS One 2008;3(8):e2986.
Zhu H, Tucker HM, Grear KE, et al. A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol. Hum Mol Genet 2007;16(14):1765-72.
Kittles RA, Weiss KM. Race, ancestry, and genes: Implications for defining disease risk. Ann Rev Genomics Hum Genet 2003;4(1):33-67.
Patel RS, Su S, Neeland IJ, et al. The chromosome 9p21 risk locusis associated with angiographic severity and progression of coronary artery disease. Eur Heart J 2010;31(24):3017-23.
Anselmi M, Garbin U, Agostoni P, et al. Plasma levels of oxidized-low-density lipoproteins are higher in patients with unstable angina and correlated with angiographic coronary complex plaques. Atherosclerosis 2006;185(1):114-20.
Sadeghi M, Heidari R, Mostanfar B, et al. The relation between ankle-brachial index (ABI) and coronary artery disease severity and risk factors: an angiographic study. ARYA Atherosclerosis 2011;7(2):68-73.
Lei W, Yi-tong Ma, Xiang X, et al. Association of MMP-9 gene polymorphisms with acute coronary syndrome in the Uygur population of China. World J Emerg Med 2011;2(2):104-10.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16(3):1215.
Sullivan DR, Marwick TH, Freedman SB. A new method of scoring coronary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. Am Heart J 1990;119(6):1262-7.
Garcia-Moll X, Coccolo F, Cole D, et al. Serum Neopterin and Complex Stenosis Morphology in Patients With Unstable Angina. J Am Coll Cardiol 2000;35(4):956-62.
Anselmi M, Garbin U, Agostoni P, et al. Plasma levels of oxidized-low-density lipoproteins are 2010 with angiographic coronary complex plaques. Atherosclerosis 2006;185(1):114-20.
Martinelli N, Girelli D, Lunghi B, et al. Polymorphisms at LDLR locus may be associated with coronary arterydisease through modulation of coagulation factor VIII activity and independently from lipid profile. Blood 2010; 116(25):5688-97.
Baudhuin LM. Genetics of coronary artery disease: focus on genomewide association studies. Am J Transl Res 2009;1(3):221-34.
| Files | ||
| Issue | Vol 52, No 5 (2014) | |
| Section | Articles | |
| Keywords | ||
| Coronary artery disease LDLR locus Single nucleotide polymorphism SMARCA4 gene | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
