Abstract
Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of triglyceride-rich lipoprotein particles (Chylomicrons and very-low-density lipoprotein). LPL polymorphisms’ effects on lipids and coronary artery disease are controversial among studies and populations. Our aim was to study the association between six polymorphisms, haplotypes and significant coronary stenosis (SCS), disease severity and lipid parameters in Tunisian patients. LPL PvuII, 93 T/G, 188 G/E, HindIII, N291S and D9N polymorphisms were analyzed in 316 patients who underwent coronary angiography. Assessment of coronary angiograms identified SCS as the presence of stenosis >50 % in at least one major coronary artery. The stenosis severity was determined by using Gensini score and vessels number. A significant association of SCS with TT of the HindIII polymorphism was showed (odds ratio (OR): 2.84, 95 % CI, 1.19–7.40, p = 0.017) and TG (OR: 1.77, 95 % CI, 1.99–2.82, p = 0.033). The mutated HindIII genotype was significantly associated with increased TG and ApoB/ApoA-I ratio and with decreased HDL-C. Haplotype analysis showed that OR of SCS associated with the CTGTAG haplotype was 2.12 (95 % CI 1.05–4.25, p = 0.032) and with CGGGAA was 0.71 (95 % CI 0.26–1.95, p = 0.022) compared to the CTGTAA. Significant difference in Gensini score was observed among HindIII genotype and haplotypes. A significant association between the mutated genotype of HindIII polymorphism and decreased HDL-C level and increased ApoB/ApoA-I ratio and TG level was showed. Our results suggest that HindIII and D9N polymorphisms and CTGTAG haplotype seem to be considered as marker of predisposition to coronary stenosis. In another hand, HindIII and haplotypes were related to stenosis severity.
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Ben romdhane H, Bougatef S, Skhiri H, Gharbi D, Kafsi MN, Belhani A et al (2004) The first Tunisian cardiovascular diseases register: processes and results. Revue d’épidémiologie ET de santé publique 52:558–564
Miller GJ, Miller NE (1975) Plasma high density lipoprotein concentration and development of ischaemic heart-disease. Lancet 1:16–25
Goldbourt U, Yaaari S, Medalie JH (1997) Isolated low HDL cholesterol as a risk factor for coronary heart disease. Arterioscler Thromb Vasc Biol 17:107–113
Stephens JW, Humphries SE (2003) The molecular genetics of cardiovascular disease: clinical implications. J Intern Med 253:120–127
Chen Q, Razzaghi H, Demirci FY, Kamboh MI (2008) Functional significance of lipoprotein lipase HindIII. Atherosclerosis 200:102–108
Kussi T, Ehnholm C, Viikari J, Harkonen R, Vartiainen E, Puska P et al (1989) Postheparin plasma lipoprotein and hepatic lipase are determinants of hypoalphalipoproteinemia and hyperalphalipoproteinemia. J Lipid Res 30:1117–1126
Patsch JR, Prasad S, Gotto AM, Patsh W (1987) 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. J Clin Invest 80:341–347
Anderson JL, King GJ, Bair TL, Elmer SP, Muhlestein JB, Habashi J et al (1999) Association of lipoprotein lipase gene polymorphisms with coronary artery disease. J Am Coll Cardiol 33:1013–1020
Su Z, Zhang S, Hou Y, Zhang Li, Liao L, Xiao C (2002) Relationship between a novel polymorphism of lipoprotein lipase gene and coronary heart disease. Chin Med J (EngI) 115:677–680
Goldberg IJ (1996) Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenisis. J Lipid Res 37:693–707
Olivecrona G, Olivecrona T (1995) Triglyceride lipases and atherosclerosis. Curr Opin Lipidol 6:291–305
Sagoo GS, Tatt I, Salanti G, Butterworth AS, Sarwar N, Maarle Mv et al (2008) Seven lipoprotein lipase gene polymorphisms, lipid fractions, and coronary disease: a HuGE association review and meta-analysis. Am J Epidemiol 168:1233–1246
Goodarzi MO, Wong H, Quinones MJ, Taylor KD, Guo X, Castellani LW, Antoine HJ, Yang H, Hsueh WA, Rotter JI (2005) The 3’ untranslated region of the lipoprotein lipase gene: haplotype structure and association with post-heparin plasma lipase activity. J Clin Endocrinol Metab 90:4816–4823
Emi M, Wilson DE, Iverius PH, Wu L, Hata A, Hegele R, Williams RR, Lalouel JM (1990) Missense mutation (Gly → Glu 188) of human lipoprotein lipase imparting functional deficiency. J Biol Chem 10:5910–5916
Hallman DM, Groenemeijer BE, Jukema JW, Boerwinkle E, Kastelein JJ (1999) Analysis of lipoprotein lipase haplotypes reveals associations not apparent from analysis of the constituent loci. Annals of human genetics. Ann Hum Genet 63:499-510.
Wang XL, Tam C, McCredie RM, Wilcken DEL (1994) Determinants of severity of coronary artery disease in Australian men and women. Circulation 89:1974–1981
Hu Y, Liu W, Huang R, Zhang X (2006) A systematic review and meta-analysis of the relationship between lipoprotein lipase Asn291Ser variant and diseases. J Lipid Res 47:1908–1914
Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG (1999) Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation 99:2901–2907
Zhang R, Liu Y, Yang LC, Bai H, Liu BW (2003) Study on lipoprotein lipase gene HindIII polymorphism in Chinese type IIb hyperlipoproteinemia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 20:539–541
Socquard E, Durlach A, Clavel C, Nazeyrollas P, Durlach V (2006) Association of HindIII and PvuII genetic polymorphisms of lipoprotein lipase with lipid metabolism and macrovascular events in type 2 diabetic patients. Diabetes Metab 32:262–269
Gigek Cde O, Chen ES, Cendoroglo MS, Ramos LR, Araujo LM, Payão SL et al (2007) Association of lipase lipoprotein polymorphisms with myocardial infarction and lipid levels. Clin Chem Lab Med 45:599–604
McGladdery SH, Pimstone SN, Clee SM, Bowden JF, Hayden MR, Frohlich JJ (2001) Common mutations in the lipoprotein lipase gene (LPL): effects on HDL-cholesterol levels in a Chinese Canadian population. Atherosclerosis 156:401–407
Brousseau ME, Goldkamp AL, Collins D, Demissie S, Connolly AC, Cupples CA et al (2004) Polymorphisms in the gene encoding lipoprotein lipase in men with low HDL-C and coronary heart disease: the Veterans Affairs HDL Intervention Trial. J Lipid Res 45:1885–1891
Van Bockxmeer FM, Liu Q, Mamotte C, Burke V, Taylor R (2001) Lipoprotein lipase D9N, N291S and S447X polymorphisms: their influence on premature coronary heart disease and plasma lipids. Atherosclerosis 157:123–129
Ferencak G, Pasalic D, Grskovic B, Cheng S, Fijal B, Sesto M et al (2003) Lipoprotein lipase gene polymorphisms in Croatian patients with coronary artery disease. Clin Chem Lab Med 41:541–546
Abu-Amero KK, Wyngaard CA, AI-Boudari OM, Kambouris M, Dzimiri N (2003) Lack of association of lipoprotein lipase gene polymorphisms with coronary artery disease in the Saudi Arab population. Arch Pathol Lab Med 127:597–600
Wang XL, McCredie RM, Wilcken DE (1996) Common DNA polymorphisms at the lipoprotein lipase gene: association with severity of coronary artery disease and diabetes. Circulation 93:1339–1345
Rejeb J, Omezzine A, Rebhi L, Naffeti I, Kchok K, Belkahla R et al (2008) Association of the cholesteryl ester transfer protein Taq1 B2B2 genotype with higher high-density lipoprotein cholesterol concentrations and lower risk of coronary artery disease in a Tunisian population. Arch Cardiovasc Dis 101:629–636
Gensini Goffredo G (1983) A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 51:606
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502
Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215
Lowontin RC (1984) The interaction of selection and linkage 1. General considerations: heterotic models. Genetics 49:49–67
Greeland S, Rothman KJ (1998) Introduction to stratified analysis. In: Williams A, Wilkins B (eds) Modern epidemiology. Lippincott, Philadelphia, PA, pp 253–279
Shagisultanova EI, Mustafina OE, Tuktarova IA, Khusnutdinova EK (2001) HindIII polymorphism of lipoprotein lipase gene and risk of myocardial infarction. Mol Gen Mikrobiol Virusol 3:18–22
Minich A, Kessling A, Roy M, Giry C, Delangavant G, Lavigne J et al (1995) Prevalence of alleles encoding defective lipoprotein lipase in hypertriglyceridemic patients of French Canadian descent. J Lipid Res 36:117–124
Arca M, Campagna F, Montali A, Barillã F, Mangicri E, Tanzilli G et al (2000) The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis. Clin Genet 58:369–374
Thorn JA, Chamberlain JC, Alcolando JC, Oka K, Chan L, Stocks J et al (1990) Lipoprotein and hepatic lipase gene variants in coronary atherosclerosis. Atherosclerosis 85:55–60
Malygina NA, Kostomarova IV, Deriagin GV, Serova LD (2002) HindIII DNA-polumorphism of lipoprotein lipase gene in elderly patients with ischemic heart disease. Ter Arkh 74:64–66
Gerdes C, Gerdes LU, Hansen PS, Faergeman O (1995) Polymorphisms in the lipoprotein lipase gene and their associations with plasma lipid concentrations in 40-year-old Danish men. Circulation 92:1765–1769
Jemaa R, Fumeron F, Poirier O, Lecerf L, Evans A, Arveiler D et al (1995) Lipoprotein lipase gene polymorphism: associations with myocardial infarction and lipoprotein levels, the ECTIM study. Etude cas Témoin sur l’infarctus du Myocarde. J Lipid Res 36:2141–2146
Talmud PJ, Bujac SR, Hall S, Miller GJ, Humphries SE (2000) Substitution of asparagines for aspartic acid at residue 9 (D9N) of lipoprotein lipase markedly augments risk of ischemic heart disease in males smokers. Atherosclerosis 149:75–81
Yang Y, Ruiz-Narvaez E, Niu T, Xu X, Campos H (2004) Genetic variants of the lipoprotein lipase gene and myocardial infarction in the Central Valley of Costa Rica. J Lipid Res 45:2106–2109
Ma YQ, Thomas GN, Ng MC, Critchley JA, Chan JC, Tomlinson B (2003) The lipoprotein lipase gene HindIII polymorphism is associated with lipid levels in early-onset type 2 diabetic patients. Metabolism 52:338–343
Razzaghi H, Aston CE, Hamman RF, Kamboh MI (2000) Genetic screening of the lipoprotein lipase gene for mutations associated with high triglyceride/low HDL-cholesterol levels. Hum Genet 107:257–267
Hall S, Talmud PJ, Cook DG, Wicks PD, Rothwell MJ, Strazzullo P et al (2000) Frequency and allelic associations of common variants in the lipoprotein lipase gene in different ethnic groups: the Wandsworth Heart and Stroke Study. Genet Epidemiol 18:203–216
Shimo-Nakanishi Y, Urabe T, Hattori N, Watanabe Y, Nagao T, Yokochi M et al (2001) Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral infarction in the Japanese. Stroke 32:14–81
Acknowledgments
We are especially grateful to the study participants. We acknowledge the technical assistance of staff members of the Biochemistry and Cardiology Departments. This study was supported by grants from the Tunisian ministry of Higher Education, Scientific Research, and Technology, and the Ministry of Health (UR 26/04).
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Lamia Rebhi and Kaouther Kchock have equally contributed to this work.
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Rebhi, L., Kchok, K., Omezzine, A. et al. Six lipoprotein lipase gene polymorphisms, lipid profile and coronary stenosis in a Tunisian population. Mol Biol Rep 39, 9893–9901 (2012). https://doi.org/10.1007/s11033-012-1856-9
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DOI: https://doi.org/10.1007/s11033-012-1856-9