Variants of D9N, G188A, N291S, and 93 T/G Genes in patients with Coronary Artery Diseases
Main Article Content
Objective: Our work aimed to study the relationship between LPL variants D9N, G188A, N291S, and 93 T/G genes and CAD in Saudi patients.
Materials and Methods: We recruited 253 CAD patients, who underwent diagnostic coronary angiography, and 207 control subjects. Several biochemical and behavioral markers were obtained, and different genotypes of LPL variants, D9N, G188E, N291S, and 93 T/G, were detected using The PCR-RFLP method.
Results: The current study found D9N genotypes, AA, AG, and GG in 71.14%, 23.72%, and 5.14% in CAD patients, respectively. the AA, AG, and GG control genotypes were found in 81.64%, 16.43%, and 1.93%, respectively. The OR of the D9N AA versus AG genotype with a 95% CI was determined to be 1.65 (1.04–2.65), (p = 0.035). The OR of the D9N AA versus AG + GG genotype with a 95% CI was 1.80 (1.16–2.81), (p = 0.009). A strong relation of the D9N AA was observed with CAD. For the G188E, N291S, 93T/G variants insignificant were observed in both CAD and control groups.
Conclusion: This study revealed the D9N variant has an association with CAD; however, no relation was detected between CAD and G188E, N291S, and 93T/G variants in the Saudi patients.
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Chen QH, Razzaghi FY, Demirci, Kamboh MI. Functional significance of lipoprotein lipase HindIII. Atherosclerosis. 2008;200:102–108.
Eckel RH. Lipoprotein lipase: a multifunctional enzyme relevant to common metabolic diseases. New England Journal of medicine. 1989;320:1060–1068.
Anderson JL, King GJ, Bair TL, Elmer SP, Muhlestein JB, Habashi J, et al. Association of lipoprotein lipase gene polymorphisms with coronary artery disease. Journal of the American College of Cardiology. 1999;33:1013–1020.
Goldberg IJ. Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenisis. Journal of Lipid Research.1996;37:693–707.
Olivecrona G, Olivecrona T. Triglyceride lipases and atherosclerosis. Current Opinion in Lipidology.1995;6:291–305.
Helkin A, Stein JJ, Lin S, Siddiqui S, Maier KG, Gahtan V, et al. Dyslipidemia Part 1-Review of Lipid Metabolism and Vascular Cell Physiology. Vascular and Endovascular Surgery. 2016;50:107–118.
Lopez Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet. 1997;349:1269–1276.
Kussi T, Ehnholm C, Viikari J, Harkonen R, Vartiainen E, Puska P, et al. Postheparin plasma lipoprotein and hepatic lipase are determinants of hypoalphalipoproteinemia and hyperalphalipoproteinemia. Journal of Lipid Research. 1989;30:1117–1126.
Patsch JR, Prasad S, Gotto AM, Patsh W. High-density lipoprotein2- relationship of the plasma levels of this lipoprotein species to its composition, to the magnitude of postprandial lipemia, and to the activities of lipoprotein lipase and hepatic lipase. Journal of Clinical Investigation. 1987;80:341–347.
Goodarzi MO, Guo X, Taylor KD, Quiñones MJ, Saad MF, Yang H, et al. Lipoprotein lipase is a gene for insulin resistance in Mexican Americans. Diabetes. 2004;53:214–220.
Bauer RC, Khetarpal SA, Hand NJ, Rader DJ. Therapeutic targets of triglyceride metabolism as informed by human genetics. Trends in Molecular Medicine. 2016;22:328–340.
Keavney B, Palmer A, Parish S, Clark S, Youngman L, Danesh J, et al. Lipid-related genes and myocardial infarction in 4685 cases and 3460 controls: discrepancies between genotype, blood lipid concentrations, and coronary disease risk. International Journal of Epidemiology. 2004;33:1002–1013.
Thorn J, Chamberlain JC, Alcolado JC, Oka K, Chan L, Stocks J, et al. Lipoprotein and hepatic lipase gene variants in coronary atherosclerosis. Atherosclerosis. 1990;85:55–60.
Peacock RE, Hamstenb A, Nilsson-Ehle P, Humphries SE. Associations between lipoprotein lipase gene polymorphisms and plasma correlations of lipids, lipoproteins and lipase activities in young myocardial infarction survivors and age-matched healthy individuals from Sweden. Atherosclerosis. 1992;97:171–185.
Wang XL, McCredie RM, Wilcken DE. Common DNA polymorphisms at the lipoprotein lipase gene: Association with severity of coronary artery disease and diabetes. Circulation. 1996;93:1339–1345.
Murthy V, Julien P, Gagne C. Molecular pathobiology of the human lipoprotein lipase gene. Pharmacology & Therapeutics. 1996;70:101–135.
Lalouel JM, Wilson DE, Iverius PH. Lipoprotein Lipase and hepatic triglyceride lipase: molecular and genetic aspects. Current Opinion in Lipidology. 1992;3:86–95.
Abdel Hamid MM, Ahmed S, Salah A, Tyrab EM, Yahia LM, Elbashir EA, et al. Associa¬tion of lipoprotein lipase gene with coronary heart disease in Sudanese population. Journal of Epidemiology and Global Health. 2015;5:405–407.
Petrescu-Dănilă, E, Voicu PM, Ionescu CR. Mutagenic aspects of the lipoprotein lipase gene. Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi. 110: 173–177.
Agirbasli M, Sumerkan MC, Eren F, Agirbasli D. The S447X variant of lipoprotein lipase gene is inversely associated with severity of coronary artery disease. Heart Vessels. 2006;26:457–463.
Mailly F, Tugrul Y, Reymer PWA, Bruin T, Seed M, Groenemeyer A,et al. A common variant in the gene for lipoprotein lipase (Asp9→Asn): functional implications and prevalence in normal and hyperlipidemic subjects. Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:468–478.
Emi M, Wilson DE, Iverius PH, Wu L, Hata A, Hegele R, et al. Missense mutation (Gly → Glu 188) of human lipoprotein lipase imparting functional deficiency. Journal of Biological Chemistry. 1990;10:5910–5916.
Reymer PWA, Gagné E, Groenemeyer BE, Zhang H, Forsyth I, Jansen JC,et al. A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis. Nature Genetics. 1995;10:28–34.
Yang Y, Ruiz-Narvaez E, Niu T, Xu X, Campos H. Genetic variants of the lipoprotein lipase gene and myocardial infarction in the Central Valley of Costa Rica. Journal of Lipid Research. 2004;45:2106–2109.
Nordestgaard BG, Abildgaard S, Wittrup HH, Steffensen R, Jensen G, Tybjrg-Hansen A. Heterozygous lipoprotein lipase deficiency: Frequency in the general population, effect on plasma lipid levels, and risk of ischemic heart disease. Circulation. 1997;96:1737–1744.
Monsalve V, Henderson H, Roederer G, Julien P, Deeb S, Kastelein JJ, et al. A missense mutation at codon 188 of the human lipoprotein lipase gene is a frequent cause of lipoprotein lipase deficiency in persons of different ancestries. Journal of Clinical Investigation. 1990;86:728-34.
Kastelein JJ, Ordovas JM, Wittekoek ME, Pimstone SN, Wilson W, Gagne SE, et al. Two common mutations (D9N, N291S) in lipoprotein lipase: A cumulative analysis of their influence on plasma lipids and lipoproteins in men and women. Clinical Genetics. 1999;56:297–305.
Rebhi L, Kchok K, Omezzine A, Kacem S, Rejeb J, Ben HadjMbarek I, et al. Six lipoprotein lipase gene polymorphisms, lipid profile and coronary stenosis in a Tunisian population. Molecular Biology Reports. 2012;39:9893–9901.
Razzaghi H, Day BW, McClure RJ, Kamboh MI. Structure-function analysis of D9N and N291S mutations in human lipoprotein lipase using molecular modelling. Journal of Molecular Graphics and Modelling. 2001;19:487–494.
Fallah S, Seifi M, Firoozrai M, Ghohari L, Samadirad B. Effect of apolipoprotein E genotypes on incidence and development of coronary stenosis in Iranian patients with coronary artery disease. Journal of Clinical Laboratory Analysis. 2011;25:43–46.
Dias A, Amália F, Claudia G, Maria D, Rafaela F, Rosemery N,et al. Severity of angiographic coronary obstruction and the apolipoprotein E polymorphism in acute coronary syndromes. Arquivos Brasileiros de Cardiologia. 2009;93:221–230.
Talmud PJ, Bujac Sr, Hall S, Miller GJ, Humphries SE. Substitution of asparagines for aspartic acid at residue 9 (D9N) of lipoprotein lipase markedly augments risk of ischemic heart disease in male’s smokers. Atherosclerosis. 2000;149:75–81.
Fisher RM, Humphries SE, Talmud PJ. Common variation in the lipoprotein lipase gene: effects on plasma lipids and risk of atherosclerosis. Atherosclerosis. 1997;135:145–159.
Syvanne M, Antikainen M, Ehnholm S, Tenkanen H, Lahdenpera S, Ehnholm C, et al. Heterozygosity for Asn291→Ser mutation in the lipoprotein lipase gene in two Finnish pedigrees: effect of hyperinsulinemia on the expression of hypertriglyceridemia. Journal of Lipid Research. 1996;37:727–738.
Brummer DD, Evans D, Berg H, Greten U, Beisiegel WA, Mann WA. Expression of type III hyperlipoproteinemia in patients homozygous for apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial hyperinsulinemia. Journal of Molecular Medicine. 1998;76:355–364.
Rios DL, Vargas AF, Ewald GM, Torres MR, Zago AJ, Callegari-Jacques SM, et al. Common variants in the lipoprotein lipase gene in Brazil: association with lipids and angiographically assessed coronary atherosclerosis. Clinical Chemistry and Laboratory Medicine. 2003;41:1351–1356.
Brousseau ME, AL Goldkamp D, Collins S, Demissi AC, Connolly LA, Cupples LA, et al. Polymorphisms in the gene encoding lipoprotein lipase in men with low HDL-C and coronary heart disease: The Veterans Affairs HDL Intervention Trial. Journal of Lipid Research. 2004;45:1885–1891.
van Bockxmeer FMQ, Liu C, Mamotte V, Burke RT. Lipoprotein lipase D9N, N291S and S447X polymorphisms: their influence on premature coronary heart disease and plasma lipids. Atherosclerosis. 2001;157:123–129.
Ferencak GD, Pasalic B, Grskovic S, Cheng B, Fijal M, Sesto JS, et al. Lipoprotein lipase gene polymorphisms in Croatian patients with coronary artery disease. Clinical Chemistry and Laboratory Medicine. 2003;41:541–546.
Sagoo GS, Tatt I, Salanti G, Butterworth AS, Sarwar N, Maarle Mv, et al. Seven lipoprotein lipase gene polymorphisms, lipid fractions, and coronary disease: a HuGE association review and meta-analysis. American Journal of Epidemiology. 2008;168:1233–1246.
McGladdery SH, Pimstone SN, Clee SM, Bowden JF, Hayden MR, Frohlich JJ. Common mutations in the lipoprotein lipase gene (LPL): effects on HDL-cholesterol levels in a Chinese Canadian population. Atherosclerosis. 2001;156:401–407.
Minich A, Kessling A, Roy M, Giry C, Delangavant G, Lavigne J, et al. Prevalence of alleles encoding defective lipoprotein lipase in hypertriglyceridemic patients of French Canadian descent. Journal of Lipid Research. 1995;36:117–124.
Arca M, Campagna F, Montali A, Barilla F, Mangicri E, Tanzilli G, et al. The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis. Clinical Genetics. 2000;58:369–374.
Wittrup HH, Tybjærg-Hansen A, Steffensen R, Deeb SS, Brunzell JD, Jensen G, et al. Mutations in the lipoprotein lipase gene associated with ischemic heart disease in men - The Copenhagen City Heart Study. Arteriosclerosis Thrombosis and Vascular Biology. 1999;6:1535-1540.
Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation. 1999;99:2901–2907.
Jemaa R1, Fumeron F, Poirier O, Lecerf L, Evans A, Arveiler D, et al. Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels, the ECTIM study. Etude Cas Témoin sur l'Infarctus du Myocarde. Journal of Lipid Research. 1995;36:2141-2146.
Funke H, Assmann G. The low down on lipoprotein lipase. Nature Genetics. 1995;10:6-7.
Jin F, Zhou H. The association of the D9N and N291S polymorphisms in LPL gene with coronary disease: a meta-analysis. International Journal of Clinical and Experimental Medicine. 2017;10(12):15896-15904.