title: Butyrylcholinesterase K variant and the APOE-epsilon 4 allele work in synergy to increase the risk of coronary artery disease especially in diabetic patients.
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-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.
authors.affiliation: 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
authors.forename: Asad
authors.initials: A
authors.lastname: Vaisi-Raygani
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Rahimi
authors.forename: Haidar
authors.initials: H
authors.lastname: Tavilani
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Pourmotabbed
mesh_terms: 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
chemical_list: D053327:Apolipoprotein E4; D008055:Lipids; D002091:Butyrylcholinesterase
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