Genetic and environmental factors that regulate cytosolic epoxide hydrolase activity in normal human lymphocytes.

Abstract

To determine whether genetic mechanisms control large variations in cytosolic epoxide hydrolase (cEH) activity of unstimulated lymphocytes from normal human subjects, cEH activity was measured in (a) 6 sets of monozygotic (MZ) twins and 6 sets of dizygotic (DZ) twins; (b) 100 unrelated male subjects; and (c) 6 families. The twin study revealed predominantly genetic control (H2(1) = 0.95). Variability was markedly less within MZ (intrapair variance = 0.25) than DZ twins (intrapair variance = 6.33). In 100 unrelated male subjects the extent of interindividual variation was 11-fold. Unimodal distribution of values among 99 subjects encompassed a sixfold range. One outlier with very high activity clearly stood apart. Using the whole distribution curve we phenotyped members of six families. In the outlier's family, analysis of three generations suggested autosomal dominant transmission of high cEH activity. Analysis of the other 5 families and of 12 sets of twins, all from the large unimodal distribution, was consistent with either monogenic or polygenic control of variations within this mode. Several temporal host factors, including fever, the menstrual cycle, a 24-h fast, and diurnal variations, were investigated. Fever and fasting elevated cEH activity. Diurnal variations produced no observable alteration. During the menstrual cycle irregular fluctuations occurred.