Association between two common polymorphisms (single nucleotide polymorphism -250G/A and -514C/T) of the hepatic lipase gene and coronary artery disease in type 2 diabetic patients

Mohammadzadeh, Ghorban; Ghaffari, Mohammad-Ali; Bazyar, Mohammad; Kheirollah, Alireza

Association between two common polymorphisms (single nucleotide polymorphism -250G/A and -514C/T) of the hepatic lipase gene and coronary artery disease in type 2 diabetic patients

Authors

¹ Hyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

² Cellular and Molecular Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

³ Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Background: Variations in the hepatic lipase (HL) gene are the potential candidate for coronary artery disease (CAD) especially in type 2 diabetes mellitus (T2DM) in diverse populations. We assessed the association of -514C/T and -250G/A polymorphisms in HL (LIPC) gene with CAD risk in Iranian population with type 2 diabetes.
Materials and methods: We evaluated 322 type 2 diabetic patients, 166 patients with normal angiograms as controls and 156 patients those identified with CAD undergoing their first coronary angiography as CAD cases. Genotyping of -514C/T and -250G/A polymorphisms in the promoter of the LIPC gene were studied by polymerase chain reaction (PCR)-restriction fragment length polymorphism technique.

Results: Genotype distributions in CAD cases (73.7%, 20.5%, and 5.8% for −250G/A) and (62.2%, 32.7%, and 5.1% for -514C/T) were significantly different from those in controls (60.8%, 37.4%, and 1.8% for -250G/A) and (51.2%, 48.2%, and 0.6% for -514C/T). CAD cases had lower A-allele frequency than controls (0.131 vs. 0.196, P = 0.028). The odds ratio for the presence of -250 (GG + GA) genotype and A allele in CAD cases were 2.206 (95% confidence interval [CI] =1.33-3.65, P = 0.002) and 1.609 (95% CI = 1.051 −2.463, P = 0.029) respectively. Haplotype analysis demonstrated a significant association between especially LIPC double mutant (−250 A/-514 T) haplotype and presence of CAD.
Conclusion: Our findings indicated that -250 G/A polymorphism rather than -514 C/T polymorphism of LIPC gene is more associated with the increased risk of CAD particularly in women with T2DM.

Keywords

References

1.	Tradif JC. Coronary artery disease in 2010. European Heart Journal Supplements 2010;12:C2-10.
2.	Wilson PW, D′Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-1847.
3.	Zdravkovic S, Wienke A, Pedersen NL, Marenberg ME, Yashin AI, De Faire U. Heritability of death from coronary heart disease: A 36-year follow-up of 20,966 Swedish twins. J Intern Med 2002;252:247-254.
4.	Jansen H, Verhoeven AJ, Sijbrands EJ. Hepatic lipase: A pro- or anti-atherogenic protein? J Lipid Res 2002;43:1352-1362.
5.	Zambon A, Austin MA, Brown BG, Hokanson JE, Brunzell JD. Effect of hepatic lipase on LDL in normal men and those with coronary artery disease. Arterioscler Thromb 1993;13:147-53.
6.	Eller P, Schgoer W, Mueller T, Tancevski I, Wehinger A, Ulmer H, et al. Hepatic lipase polymorphism and increased risk of peripheral arterial disease. J Intern Med 2005;258:344-8.
7.	Cai SJ, Wong DM, Chen SH, Chan L. Structure of the human hepatic triglyceride lipase gene. Biochem 1989;28:8966-71.
8.	Ameis D, Stahnke G, Kobayashi J, McLean J, Lee G, Büscher M, et al. Isolation and characterization of the human hepatic lipase gene. J Biol Chem 1990;265:6552-5.
9.	Guerra R, Wang J, Grundy SM, Cohen JC. A hepatic lipase (LIPC) allele associated with high plasma concentrations of high density lipoprotein cholesterol. Proc Natl Acad Sci USA 1997;94:4532-7.
10.	Murtomaki S, Tahvanainen E, Antikainen M, Tiret L, Nicaud V, Jansen H. et al. Hepatic lipase gene polymorphisms influence plasma HDL levels. Results from Finnish EARS participants. European Atherosclerosis Research Study. Arterioscler Thromb Vasc Biol 1997;17:1879-4.
11.	Bertolini S, Pisciotta L, Di Scala L, Langheim S, Bellocchio A, Masturzo P, et al. Genetic polymorphisms affecting the phenotypic expression of familial hypercholesterolemia. Atherosclerosis 2004;174:57-65.
12.	Jiménez-Gómez Y, Pérez-Jiménez F, Marín C, Gómez P, Moreno R, Delgado J, et al. The -250G/A polymorphism in the hepatic lipase gene promoter influence the postprandial lipemic response in healthy men. Nutr Metab Cardiovasc Dis 2008;18:173-81.
13.	Ko YL, Hsu LA, Hsu KH, Ko YH, Lee YS. The interactive effects of hepatic lipase gene promoter polymorphisms with sex and obesity on high density- lipoprotein cholesterol levels in Taiwanese-Chinese. Atherosclerosis 2004;172:135-42.
14.	Lindi V, Schwab U, Louheranta A, Vessby B, Hermansen K, Tapsell L, et al. The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study. Nutr Metab Cardiovasc Dis 2008;18:88-95.
15.	Pihlajamaki J, Karjalainen L, Karhapaa P, Vauhkonen I, Taskinen MR, Deeb SS, et al. G-250A substitution in promoter of hepatic lipase gene is associated with dyslipidemia and insulin resistance in healthy control subjects and in members of families with familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol 2000;20:1789-95.
16.	Stancakova A, Baldaufova L, Javorsky M, Kozarova M, Salagovic J, Tkac I. Effect of gene polymorphisms on lipoprotein levels in patients with dyslipidemia of metabolic syndrome. Physiol Res 2006;55:483-90.
17.	Wood KC, Fullerton MD, El-Sohemy A, Bakovic M. Interactions between hepatic lipase and apolipoprotein E gene polymorphisms affect serum lipid profiles of healthy Canadian adults. Appl Physiol Nutr Metab 2008;33:761-8.
18.	Zhao S, Xie X, Nie S. The -250G/A polymorphism in the human hepatic lipase gene promoter affects blood lipids in Chinese. Clin Chim Acta 2006; 365:149-52.
19.	de Andrade FM, Silveira FR, Arsand M, Antunes AL, Torres MR, Zago AJ, et al. Association between -250G/A polymorphism of the hepatic lipase gene promoter and coronary artery disease and HDL-C levels in a Southern Brazilian population. Clin Genet 2004;65:390-5.
20.	Wei M, Lu YS, Li PP. Association of the hepatic lipase gene -250G/A promoter polymorphism with the susceptibility to type 2 diabetes mellitus combining with coronary heart disease. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2009;26:219-22.
21.	Zambon A, Deeb SS, Hokanson JE, Brown BG, Brunzell JD. Common variants in the promoter of the hepatic lipase gene are associated with lower levels of hepatic lipase activity, buoyant LDL, and higher HDL ₂ cholesterol. Arterioscler Thromb Vasc Biol 1998;18:1723-9.
22.	Tahvanainen E, Syvanne M, Frick MH, Murtomaki-Repo S, Antikainen M, Kesaniemi YA, et al. Association of variation in hepatic lipase activity with promoter variation in the hepatic lipase gene. The LOCAT Study Investigators. J Clin Invest 1998; 101:956-60.
23.	Hegele RA, Harris SB, Brunt JH, Young TK, Hanley AJ, Zinman B, et al. Absence of association between genetic variation in the LIPC gene promoter and plasma lipoproteins in three Canadian populations. Atherosclerosis 1999;146:153-60.
24.	Shohet RV, Vega GL, Anwar A, Cigarroa JE, Grundy SM, Cohen JC. Hepatic lipase (LIPC) promoter polymorphism in men with coronary artery disease. Allele frequency and effects on hepatic lipase activity and plasma HDL-C concentrations. Arterioscler Thromb Vasc Biol 1999;19:1975-8.
25.	Deeb SS, Zambon SS, Carr MC, Ayyobi AF, Brunzell JD. Hepatic lipase and dyslipidemia: Interactions among genetic variants, obesity, gender, and diet. J Lipid Res 2003;44:1279-86.
26.	Botma GJ, Verhoeven AJ, Jansen H. Hepatic lipase promoter activity is reduced by the C-480T and G-216A substitutions present in the common LIPC gene variant, and is increased by upstream stimulatory factor. Atherosclerosis 2001;154:625-32.
27.	Deeb SS, Peng R. The C-514T polymorphism in the human hepatic lipase gene promoter diminishes its activity. J Lipid Res 2000;41:155-8.
28.	Kashani MA, Azizi F, Hedayati M, Daneshpour MS, Shamshiri AR, Siassi F. Association between CETP Taq1B and LIPC -514C/T polymorphisms with the serum lipid levels in a group of Tehran′s population: A cross sectional study. Lipids in Health and Disease 2010;9:96-103.
29.	Zhang C, Ridaura RL, Rimm EB, Rifai N, Hunter DJ, Hu FB. Interactions between the -514C/T polymorphism of the hepatic lipase gene and life style factors in relation to HDL concentrations among US diabetic men. AmJ Clin Nut 2005;81:1429-35.
30.	Wang HR, Jiang M and Qiu JP. Quantitative Assessment of the Effect of Hepatic Lipase Gene Polymorphism on the Risk of Coronary Heart Disease. Archives of Medical Research 2010;41:383-390.
31.	Ghaffari MA, Askari Sede S, Rashtchizadeh N, Mohammadzadeh G, Majidi S. Association of CRP gene polymorphism with CRP levels and Coronary Artery Disease in Type 2 Diabetes in Ahvaz, southwest of Iran. BioImpacts 2014; 4:133-139.
32.	Rashtchizadeh N, Askari Sede S, Ghaffari MA, Mohammadzadeh G, Majidi S. Associations of pentraxin 3 with presence and severity of coronary artery disease in type 2 diabetes patients. Turk J Biochem 2015;40:37-43.
33.	Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Research 1988;16:1215.
34.	Andersenn RV, Wittrup HH, Tybaerg-Hansen A, Steffensen R, Schnohr P, Nor destgaard BG. Hepatic lipase mutations, elevated high-density lipoprotein cholesterol, and increased risk of ischemic heart disease the Copenhagen City Heart Study. J Am Coll Cardiol 2003;41:1972-82.
35.	Dugi KA, Brandauer K, Schmidt N, Nau B, Schneider JG, Mentz S, et al. Low hepatic lipase activity is a novel risk factor for coronary artery disease. Circulation 2001;104:3057-62.
36.	Roberts CK, Ng C, Hama S, Eliseo AJ, Barnard RJ. Effect of a short-term diet and exercise intervention on inflammatory/anti-inflammatory properties of HDL in overweight/obese men with cardiovascular risk factors. J Appl Physiol 2006;101:1727-32.
37.	Ansell BJ, Fonarow GC, Fogelman AM. The paradox of dysfunctional high-density lipoprotein. Curr Opin Lipidol 2007;18:427-34.
38.	Valdivielso P, José Ariza M, Vega-Román C, González-Alegre T, Rioja J, Ulzurrun E, et al. Association of the -250G/A promoter polymorphism of the hepatic lipase gene with the risk of peripheral arterial disease in type 2 diabetic patients. Journal of Diabetes and Its Complications 2008;22:273-77.
39.	Jansen H, Verhoeven A, Weeks L, Kastelein J, Halley D, van den Ouweland A, et al. Common C-to-T substitution at position -480 of the hepatic lipase promoter associated with a lowered lipase activity in coronary artery disease patients. Arterioscler Thromb Vasc Biol 1997;17:2837-42.
40.	Zhang C, Lopez-Ridaura R, Rimm EB, Hunter T, Hu FB. Genetic variation in the hepatic lipase gene and the risk of coronary heart disease among US diabetic men: Potential interaction with obesity. Diabetologia 2006;49:1552-9.
41.	Ji J, Herbison CE, Mamotte CD, Burke V, Taylor RR, van Bockxmeer FM. Hepatic lipase gene − 514 C/T polymorphism and premature coronary heart disease. J Cardiovasc Risk 2002;9:105-13.
42.	Fan Y, Laaksonen R, Janatuinen T, Vesalainen R, Nuutila P, Koivula T, et al. Hepatic lipase gene variation is related to coronary reactivity in healthy young men. Eur J Clin Invest 2001;31:574-80.
43.	Isaacs A, Sayed-Tabatabaei FA, Njajouo T, Witteman JC, vanDuijn CM. The -514 C/T hepatic lipase promoter region polymorphism and plasma lipids: A meta-analysis. J Clin Endocrinol Metab 2004;89:3858-63.
44.	Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, KannelWB. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 1986;256:2835-8.
45.	Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, et al. Atherosclerosis Risk in Communities Study Group. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein (a), apolipoproteins A-I and B, and HDL density sub fractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 2001;104:1108-13.
46.	Grarup N, Andersen G. Gene-environment interactions in the pathogenesis of type 2 diabetes and metabolism. Curr Opin Clin Nutr Metab Care 2007;10:420-6.
47.	Austin M, Breslow J, Hennekens C, Buring J, Willett W, Krauss R. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 1988;13:1917-21.

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