Abstract
We have previously shown that butyrylcholinesterase-K (BCHE-K, G1615A/Ala539Thr) variant increases the risk of coronary artery disease (CAD). In addition, we have found that the presence of APOE-ε4 allele augments the risk of CAD in patients with type II diabetes mellitus (T2DM/CAD). Here we explored the concomitant presences of two alleles of the BCHE-K and APOE-ε4 in increasing the risk of CAD or diabetes in T2DM patients with or without CAD and CAD patients without T2DM. This case–control study comprised 631 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: type II diabetic patients with no sign of CAD (T2DM), type II diabetic patients with CAD/ND (T2DM/CAD), CAD patients with no sign of diabetes (CAD/ND), and healthy individuals (NCAD/ND). BCHE-K variant and APOE genotypes were detected by PCR-RFLP and serum lipid level was measured enzymatically. We found that BCHE-K and APOE-ε4 allele act synergistically to increase the risk of CAD in both T2DM, non-diabetic and total CAD (TCAD = T2DM/CAD + CAD/ND) individuals. The level of synergy 1.5 and 1.2 fold are higher in CAD patients (OR = 4.5; P = 0.011) with T2DM than the non-diabetic CAD patients (OR = 3.07; P = 0.024) and TCAD patients (OR = 3.74; P = 0.018), respectively. The CAD subjects with and without T2DM and TCAD patients carrying both APOE-ε4 allele and BCHE-K had significantly lower plasma HDL-C (P values = 0.008, 0.047, and 0.036, respectively) and higher plasma LDL-C (P values = 0.025, 0.048, and 0.04, respectively), than that of the control carriers both APOE-ε4 and BCHE-K. We have found that BCHE-K and APOE-ε4 allele not only act synergistically to increase the risk of CAD, particularly in T2DM subjects in population from western Iran, who have high levels of LDL-C and low levels of HDL-C, suggesting that a specific therapeutic intervention should be considered for these particular groups of patients.
Similar content being viewed by others
References
Kalix S, Meynet MCB, Garin MCB, James RW (2001) The apolipoprotein e2 allele and the severity of coronary artery disease in Type 2 diabetic patients. Diabet Med 18:445–450
Mahfouz RAR, Sabbagh AS, Zahed LF, Mahfoud ZR, Kalmoni RF, Otrock ZK, Taher AT, Zaatari GS (2006) Apolipoprotein E gene polymorphism and allele frequencies in the Lebanese population. Mol Bio Rep 33:145–149
Jaikaran ETAS, Clark A (2001) Islet amyloid and Type 2 diabetes: from molecular misfolding to islet pathophysiology. Biochim Biophys Acta 1537:179–203
Zimmet PZ (1999) Diabetes epidemiology as a tool to trigger diabetes research and care. Diabetologia 42:499–518
Hirashiki A, Yamada Y, Murase Y, Suzuki Y, Kataoka H, Morimoto Y, Tajika T, Murohara T, Yokota M (2004) Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors. J Am Coll Cardiol 44(1):209–210
Nassar BA, Rockwood K, Kirkland SA, Ransom TP, Darvesh S, Macpherson K, Johnstone DE, O’Neill BJ, Bata IR, Andreou P, Jeffery JS, Cox JL, Title LM (2006) Improved prediction of early-onset coronary artery disease using APOE epsilon4, BChE-K, PPARgamma2 Pro12 and ENOS T-786C in a polygenic model. Clin Biochem 39(2):109–114
Nassar BA, Darvesh S, Bevin LD, Rockwood K, Kirkland SA, O’neill BJ, Bata IR, Johnstone DE, Title LM (2002) Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E epsilon 4 genes in early-onset coronary artery disease. Clin Biochem 35(3):205–209
Hashim Y, Shepherd D, Wiltshire S, Holman RR, Levy JC, Clark A, Cull CA (2001) Butyrylcholinesterase K variant on chromosome 3 q is associated with Type II diabetes in white caucasian subjects. Diabetologia 44:2227–2230
Kharrazi H, Vaisi Raygani A, Sabokroh AR, Pourmotabbed T (2006) Association between apolipoprotein E polymorphism and coronary artery disease in the Kermanshah population in Iran. Clin Biochem 39:613–616
Vaisi Raygani A, Rahimi Z, Nomani H, Tavilani H, Pourmotabbed T (2006) The presence of apolipoprotein å4 and å2 alleles augments the risk of coronary artery disease in type 2 diabetic patients. Clin Biochem 40:1150–1156
Vaisi Raygani A, Rahimi Z, Entezami H, Kharrazi H, Bahrhemand F, Tavilani H, Rezaei M, Kiani A, Nomanpour B, Tavilani H, Pourmotabbed T (2008) Butyrylcholinesterase K variants increase the risk of coronary artery disease in the population of western Iran. Scandin J Clin and Lab Invest 68(2):123–129
Lepienski LM, Alcantara VM, Souza RL, Rea RR, Chautard-Freire-Maia EA (1993) Variant K of butyrylcholinesterase and types 1 and 2 of diabetes mellitus. Clin Sci Lond 85(1):77–81
Raygani AV, Zahrai M, Solt Anzadeh A, Doosti M, Javadi E, Pourmotabbed T (2004) Analysis of association between butyrylcholinesterase K variant and apolipoprotein E genotypes in alzheimer’s disease. Neurosci Lett 371(2–3):142–146
WHO (1999) Study Group Report of a WHO consultation: part 1: diagnosis and classification of diabetes mellitus. World Health Organization, Geneva
Johan SWM, Weitzner G, Rozen R (1991) A rapid procedure for extracting genomic DNA from leukocytes. Nucleic Acids Res 19:408
Jenese FS, Nielsen LR, Schwartz M (1996) Detection of the plasma cholinesterase K variant by PCR using amplification–created restriction site. Hum Heard 46:26–31
Wenham PR, Price WH, Blandell G (1991) Apolipoprotein E genotyping by onstage PCR. Lancet 337:1158–1159
Humphries SE, Ridker PM, Talmud PJ (2004) Genetic testing for cardiovascular disease susceptibility: a useful clinical management tool or possible misinformation. Arterioscler Thromb Vasc Biol 24:628–636
Saito M, Eto M, Nitta H, Kanda Y, Shigeto M, Nakayama K, Tawaramoto K, Kawasaki F, Kamei S, Kohara K, Matsuda M, Matsuki M, Kaku K (2004) Effect of apolipoprotein E4 allele on plasma LDL cholesterol response to diet therapy in type 2 diabetic patients. Diabetes Care 27(6):1276–1280
Lehmann DJ, Nagy Z, Litchfield S, Cortina Borja M, Smith DA (2000) Association of butyrylcholinesterase K variant with cholinesterasepositive neuritic plaques in the temporal cortex in late-onset alzheimer’s disease. Hum Genet 106:447–452
Abbott CA, Mackness MI, Kumar S, Olukoga AO, Gordon C, Arrol S, Bhatnagar D, Boulton AJ, Durrington PN (1993) Relationship between butyrylcholiesterase activity, hypertriglyceridemia and insulin sensitivity in diabetes mellitus. Clin Sci 85:77–81
Duman BS, Ozturk M, Yilmazer S, Hatemi H (2004) Apolipoprotein E polymorphism in Turkish subjects with Type 2 diabetes mellitus: allele frequency and relation to serum lipid concentrations. Diabetes Nutr Metab 7(5):267–274
Isbir T, Yilmaz H, Agachan B, Karaali ZE (2003) Cholesterol ester transfer protein, apolipoprotein E and lipoprotein lipase genotypes in patients with coronary artery disease in the Turkish population. Clin Genet 64(3):228–234
Lepienski LM, Souza RL, Chautard-Freire-Maia EA, Alcantara VM, Rea RR (2006) Variant K of butyrylcholinesterase and risk of early-onset type 1 diabetes mellitus in Euro-Brazilians. Diabetes Obes Metab 8(6):709–711
Corbo RM, Vilardo T, Ruggeri M, Gemma AT, Scacchi R (1999) Apolipoprotein E genotype and plasma levels in coronary artery disease. a case control study in the Italian population. Clin Biochem 32(3):217–222
Guang-da X, Xiang-Jiu Y, Lin-Shuang Z, Zhi-Song C, Yu-Sheng H (2005) Apolipoprotein e4 allele and the risk of CAD death in type 2 diabetes mellitus with ischaemia electrocardiographic change. Diabetes Res Clin Pract 68(3):223–229
Johansen A, Nielsen EM, Andersen G, Hamid YH, Jensen DP, Glumer C, Drivsholm T, Borch-Johnsen K, Jorgensen T, Hansen T, Pedersen O (2004) Large-scale studies of the functional K variant of the butyrylcholinesterase gene in relation to Type 2 diabetes and insulin secretion. Diabetologia 47(8):1437–1441
Wilson PWF, Schaefer EJ, Larson MG, Ordovas JM (1996) Apolipoprotein E alleles and risk of coronary disease: a meta-analysis. Arterioscler Thromb Vasc Biol 16:1250–1255
Mero N, Malmstrom R, Steiner G, Taskinen MR, Syvanne M (2000) Postprandial metabolism of apolipoprotein B-48- and B-100-containing particles in type 2 diabetes mellitus: relations to angiographically verified severity of coronary artery disease. Atherosclerosis 150:67–177
Ou T, Yamakawa-Kobayashi K, Arimani T et al (1998) Methylenetetrahydrofolate reductase and apolipoprotein E polymorphisms are independent risk factors for coronary heart disease in Japanese: a case–control study. Atherosclerosis 137:23–28
Gensini GF, Comeglio M, Colella A (1998) Classical risk factors and emerging elements in the risk profile for coronary artery disease. Eur Heart J 19(A):53–61
Singh PP, Naz I, Gilmour A, Singh M, Mastana S (2006) Association of APOE (Hha1) and ACE (I/D) gene polymorphisms with type 2 diabetes mellitus in north west India. Diabetes Res Clin Pract 74:95–102
Powell DS, Maksoud H, Charge SB, Moffitt JH, Desai M, Da Silva Fihlo RL et al (2003) Apolipoprotein E genotype, islet amyloid deposition and severity of Type 2 diabetes. Diab Res Clin Pract 60:105–110
Souza DR, Nakachima L, Biagioni RB, Nakazone MA, Pinhel MA, Trindade DM, Mafra VT, Tacito LH, Martin JF, Pinheiro Junior S, Brandao AC (2007) Relevance of apolipoprotein E4 for the lipid profile of Brazilian patients with coronary artery disease. Braz J Med Biol Res 40(2):189–197
Altamirano CV, Bartels CF, Lockridge O (2000) The butyrylcholinesterase K-variant shows cellular protein turnover and quaternary interaction to the wild-type enzyme. J Neurochem 74:869–877
Thomas T, Thomas G, Mclendon C, Sutton T, Mullan M (1996) β-amyloid mediated vasoactivity, and vascular endothelial damage. Nature 380:168–171
Randell EW, Mathews MS, Zhang H, Seraj JS, Sun G (2005) Relationship between serum butyrylcholinesterase and the metabolic syndrome. Clin Biochem 38:799–805
Vaisi Raygani A, Tavilani H, Rahimi Z, Zahrai M, Sheikh N, Aminian M, Pourmotabbed T (2009) Serum butyrylcholinesterase activity and phenotype associations with lipid profile in stroke patients. Clin Biochem 42:210–214
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vaisi-Raygani, A., Rahimi, Z., Tavilani, H. et al. Butyrylcholinesterase K variant and the APOE-ε4 allele work in synergy to increase the risk of coronary artery disease especially in diabetic patients. Mol Biol Rep 37, 2083–2091 (2010). https://doi.org/10.1007/s11033-009-9666-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-009-9666-4