Received on December 12, 2005
Accepted on March 9, 2006

Molecular Diagnostics and Genetics

Pseudocholinesterase: Association with the Metabolic Syndrome and Identification of 2 Gene Loci Affecting Activity

¹ Department of Medicine, University of California at San Diego School of Medicine, and VA San Diego Healthcare System, La Jolla, CA
² The Queensland Institute of Medical Research, Brisbane, Australia
³ Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
⁴ The Queensland Institute of Medical Research, Brisbane, Australia, and Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, Australia

^* To whom correspondence should be addressed. E-mail: John.Whitfield{at}email.cs.nsw.gov.au.

Background: Plasma cholinesterase activity is known to be correlated with plasma triglycerides, HDL- and LDL-cholesterol, and other features of the metabolic syndrome. A role in triglyceride metabolism has been proposed. Genetic variants that decrease activity have been studied extensively, but the factors contributing to overall variation in the population are poorly understood. We studied plasma cholinesterase activity in a sample of 2200 adult twins to assess covariation with cardiovascular risk factors and components of the metabolic syndrome, to determine the degree of genetic effects on enzyme activity, and to search for quantitative trait loci affecting activity.

Methods and Results: Cholinesterase activity was lower in women than in men before the age of 50, but increased to activity values similar to those in males after that age. There were highly significant correlations with variables associated with the metabolic syndrome: plasma triglyceride, HDL- and LDL-cholesterol, apolipoproteins B and E, urate, and insulin concentrations; -glutamyltransferase and aspartate and alanine aminotransferase activities; body mass index; and blood pressure. The heritability of plasma cholinesterase activity was 65%. Linkage analysis with data from the dizygotic twin pairs showed suggestive linkage on chromosome 3 at the location of the cholinesterase (BCHE) gene and also on chromosome 5.

Conclusions: Our results confirm and extend the connection between cholinesterase, cardiovascular risk factors, and metabolic syndrome. They establish a substantial heritability for plasma cholinesterase activity that might be attributable to variation near the structural gene and at an independent locus.