Butyrylcholinesterase K variants increase the risk of coronary artery disease in the population of western Iran

Abstract

The conflicting results of several studies suggest that there is an association between the butyrylcholinesterase-K variant (BCHE-K, G1615A/Ala539Thr) and the risk of developing coronary artery disease (CAD) in diabetes and non-diabetic subjects. The objective of this study was to determine whether the presence of the BCHE-K variant exacerbates the risk of CAD in patients from western Iran with and without type 2 diabetes mellitus (T2DM). This case-control study comprised 464 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: CAD+T2DM+ (CAD/T2DM), CAD+DM(-) (CAD/ND), CAD(-)DM+ (T2DM/NCAD) and CAD(-)DM(-)(control). The BCHE-K variant was detected by PCR-RFLP. The BCHE-K allele frequency in CAD patients with and without T2DM [total CAD (TCAD)] and separately for each group (CAD/T2DM and CAD/ND) was significantly higher than in the control group (21.1 % versus 13.3 % (p = 0.001), 22.4 % versus 13.3 % (p = 0.001) and 19.7 % versus 13.3 % (p = 0.015), respectively). The odds ratios (ORs) for the BCHE-K heterozygous and homozygous variants in TCAD subjects were 1.65 (95 % CI 1.17-2.3; p = 0.004) and 4.3 (1.05-19.4; p = 0.048); for CAD/T2DM individuals 1.76 (1.2-2.6; p = 0.004) and 4.73 (0.96-23.3; p = 0.052); and for CAD/ND patients 1.53 (1.05-2.3; p = 0.029) and 3.88 (0.8-19.7; p = 0.7), respectively. The OR of the BCHE-K allele was found to be 1.74 (1.1-2.4; p = 0.001) in TCAD subjects, 1.87 (1.12-1.48; p = 0.001) in the CAD/T2DM group and 1.59 (1.04-1.4; p = 0.016) in CAD/ND subjects. These data suggest that the BCHE-K allele increases the risk of CAD in the population (with and without DM) in western parts of Iran, and its presence intensifies the risk of CAD in T2DM. The fact that the BCHE-K allele, even in the heterozygous form, exacerbates the risk of CAD in this population, suggests that a specific therapeutic intervention should be considered for this particular group of patients.

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

“…K‐variant has a homozygous frequency 1–4%, with about a 20% frequency among Caucasians 17 . Moreover, the structure of K‐variant has a high propensity for β sheet formation, which might be related to amyloid genesis 27 …”

Review of the Toxicology of Chlorpyrifos With an Emphasis on Human Exposure and Neurodevelopment

“…Serum BuChE activity was associated with parameters of adiposity, serum lipid profile, and degree of insulin resistance in Japanese subjects (Iwaskai et al, 2007); however, BuChE(−/−) mice were at risk for obesity when placed on a high fat diet (Li et al, 2008). A large case-control study of Iranian subjects with and without type II diabetes concluded that the BuChE-K allele, even in the heterozygous form, exacerbates the risk of coronary artery disease (Vaisi-Raygani et al, 2008) Thus, although there is no established phenotype associated with decreased (or even complete lack of) BuChE activity in plasma of humans, there is certainly evidence that reduced activity of BuChE in plasma can greatly enhance susceptibility to certain drugs (e.g., succinylcholine and mivacarium) and plantderived toxins (Solanaceae alkaloids) that are substrates for BuChE. Furthermore, the tissue-specific expression and other putative functional roles for BuChE, especially a potential role in neurodevelopment, argue that inhibition of BuChE should be considered as a potential adverse effect.…”

Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome

“…We also found that a peptide derived from the C-terminal sequence of BChE-U, the ‘usual’ variant of the enzyme, was more potent in attenuating this oligomerization than a peptide derived from the C-terminal sequence of BChE-K, the ‘Kalow’ variant of the enzyme with lowered cholinesterase activity [ 23 ]. Interestingly, BChE-K has also been proposed to be a risk factor for T2DM and coronary artery disease [ 24 , 25 ]. Our Aβ findings raised the possibility that BChE could similarly attenuate the formation of amylin fibrils, so that its transient increase would serve a protective function in delaying the shift from MetS to T2DM.…”