Butyrylcholinesterase K variant and the APOE-epsilon 4 allele work in synergy to increase the risk of coronary artery disease especially in diabetic patients.
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-epsilon 4 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-epsilon 4 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-epsilon 4 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-epsilon 4 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-epsilon 4 and BCHE-K. We have found that BCHE-K and APOE-epsilon 4 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.
Vaisi-Raygani
Asad
A
Department of Clinical Biochemistry, Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Daneshgah Avenue, P.O. Box 67148, Kermanshah, 69914, Iran. vaisira@yahoo.com
Rahimi
Zohreh
Z
Tavilani
Haidar
H
Pourmotabbed
Tayebeh
T
D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D002091:Butyrylcholinesterase / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007492:Iran; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012727:Sex Characteristics
D053327:Apolipoprotein E4; D008055:Lipids; D002091:Butyrylcholinesterase
Clin Biochem. 2007 Oct;40(15):1150-6
17689519
Braz J Med Biol Res. 2007 Feb;40(2):189-97
17273655
Clin Biochem. 2006 Jun;39(6):613-6
16545358
Scand J Clin Lab Invest. 2008;68(2):123-9
17852836
Mol Biol Rep. 2006 Jun;33(2):145-9
16817024
Clin Biochem. 2006 Feb;39(2):109-14
16298355
Clin Genet. 2003 Sep;64(3):228-34
12919138
Clin Biochem. 2002 May;35(3):205-9
12074828
Diabetes Obes Metab. 2006 Nov;8(6):709-11
17026497
Hum Hered. 1996 Jan-Feb;46(1):26-31
8825459
Diabetologia. 2001 Dec;44(12):2227-30
11793025
Diabetologia. 2004 Aug;47(8):1437-41
15258737
Diabetes Nutr Metab. 2004 Oct;17(5):267-74
16295048
Neurosci Lett. 2004 Nov 23;371(2-3):142-6
15519745
Clin Biochem. 2005 Sep;38(9):799-805
15907830
Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):628-36
14715642
Diabetes Res Clin Pract. 2006 Oct;74(1):95-102
16621107
Biochim Biophys Acta. 2001 Nov 29;1537(3):179-203
11731221
Clin Biochem. 1999 Apr;32(3):217-22
10383084
Clin Biochem. 2009 Feb;42(3):210-4
19028482
Diabetologia. 1999 May;42(5):499-518
10333041
J Am Coll Cardiol. 2003 Oct 15;42(8):1429-37
14563588
Atherosclerosis. 2000 May;150(1):167-77
10781648
Nature. 1996 Mar 14;380(6570):168-71
8600393
J Neurochem. 2000 Feb;74(2):869-77
10646540
Clin Sci (Lond). 1993 Jul;85(1):77-81
8149699
Diabetes Res Clin Pract. 2003 May;60(2):105-10
12706318
Diabetes Care. 2004 Jun;27(6):1276-80
15161775
Nucleic Acids Res. 1991 Jan 25;19(2):408
2014181
Eur Heart J. 1998 Feb;19 Suppl A:A53-61
9519344
Diabet Med. 2001 Jun;18(6):445-50
11472462
Lancet. 1991 May 11;337(8750):1158-9
1674030
Diabetes Res Clin Pract. 2005 Jun;68(3):223-9
15936464
Hum Genet. 2000 Apr;106(4):447-52
10830913
Arterioscler Thromb Vasc Biol. 1996 Oct;16(10):1250-5
8857921
Atherosclerosis. 1998 Mar;137(1):23-8
9568733