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

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.

Reproducibility of antipyrine half-lives in elderly subjects.

Antipyrine half-life determined on three to five separate occasions over a period ranging from 3 weeks to 1 year was highly reproducible in each of 20 elderly subjects (12 women and 8 men; mean age, 83 years). The mean within-subject coefficient of variation for antipyrine half-life was 9.6%, whereas the between-subject coefficient of variation was 33.3%. These findings indicate high reproducibility of individual rates of drug metabolism in medically stable elderly subjects.