Relation between butyrylcholinesterase K variant, paraoxonase 1 (PON1) Q and R and apolipoprotein E ε4 genes in early-onset coronary artery disease

Objectives: The common K variant of butyrylcholinesterase (BChE-K), an enzyme which metabolizes acetylcholine and organophosphates, has been associated with Alzheimer's disease, especially in the presence of the apolipoprotein E epsilon4 allele (APOE-epsilon4). Although APOE-epsilon4 has been associated with the development of coronary artery disease (CAD). an association between the BChE-K variant and CAD has not been explored. Paraoxonase 1 (PON1), located within HDL. is an enzyme which also metabolizes organophosphates and may be antiatherogenic. The R192 variant of PON1 (PON1-R) has been associated with CAD. Design and methods: To determine whether BChE-K is also associated with premature CAD. we examined the frequency of BChE-K among patients with early-onset CAD (n = 150; < 50 yr) vs. late-onset CAD (n = 150; > 65 yr) by molecular analysis. We also examined the frequency of the PON1-R allele in both groups. and explored whether there was synergism between BChE-K and APOE-epsilon4, BChE-K and PON1-R or PON1-R and APOE-epsilon4. Results: The frequency of the BChE-K allele tended to be greater among early-onset CAD patients compared to late-onset CAD patients (41.3% vs. 31.3%: p = 0.07), but without any significant difference between males and females. There was no difference in the prevalence of the PON1-R allele between those with early- or late-onset CAD (46.0% vs. 52.7%; p = 0.25). Twenty-two patients with early-onset CAD had both the BChE-K plus APOE-epsilon4 alleles (14.7%) compared to 11 late-onset CAD patients (7.3%) (p = 0.04). There was no such association between BChE-K and PON1-R, nor PON1-R and APOE-epsilon4. Conclusions: Our study suggests that there is a minor association between BChE-K and early-onset CAD. especially in the presence of the APOE-epsilon4 allele. (C) 2002 The Canadian Society of Clinical Chemists. All rights reserved.