0921-972x/93/7703-0794$03.00/0 Journal of Clinical Endocrinology and Metabolism Copyright 0 1993 by The Endocrine Society Vol. 77, No. 3 Printed in U.S.A. Genetic Influences on Plasma Human Twins Catecholamines in P. D. WILLIAMS, I. B. PUDDEY, L. J. BEILIN, AND R. VANDONGEN University of Western Australia, Department of Medicine, Royal Perth Hospital, Perth, Western Australia, Australia ABSTRACT We examined the relative genetic and environmental influences on the variability in plasma epinephrine, norepinephrine, and dopamine levels in 109 twin pairs. Epinephrine levels were lower in females (P = 0.048). The norepi- nephrine concentration increased with age (r = 0.40; P < 0.001). Blood pressure (BP) was not associated with epinephrine levels in either sex or with norepinephrine levels in females. In males, there was a positive association between norepinephrine concentration and diastolic BP (r = 0.31; P = 0.020). A negative association between dopamine levels and systolic and diastolic BP in females (r = -0.22; P = 0.014 and r = -0.20; P = 0.027, respectively) was not maintained after accounting for age, body mass index, and sex. Using path analysis and maximum likelihood model fitting, genetic, unique environment, and age effects contributed 57% (P 5 O.OOl), 27% (P 5 O.OOl), and 16% (P 5 0.001) to the variability in norepinephrine, respectively. Genetic effects explained 64% (P < 0.1) and 74% (P < 0.1) of the variability in epinephrine concentrations in females and males, respectively. Unique environmental influences explained the remainder. Genetic and unique environmental effects explained 72% (P < 0.01) and 28% (P I 0.001) of the variability in dopamine levels. These results indicate a substantial genetic influence on plasma catecholamine levels. Although consistent associations between plasma catecholamines and BP were not evident in this study, the observed genetic influence on circulating catecholamines may be relevant to the potential role of the sympathetic nervous system in the early stages of essential hypertension. (J Clin Endocrinol Metab 77: 794-799,1993) G IVEN the importance of the sympathetic nervous sys- tem in the regulation of blood pressure (BP), both at rest and during times of stress, it is likely to play a patho- physiological role in the development of essential hyperten- sion in some individuals (1). Generally, circulating venous plasma levels of norepinephrine and its metabolites have been used to reflect overall sympathetic neural activity, al- though the validity of this assumption is subject to continuing debate (1, 2). Elevated plasma catecholamines have been reported in both established essential hypertension and bor- derline hypertension (3-5). This has not been consistently demonstrated, and the possibility that these differences were due to inadequate matching of control subjects, particularly for age, has been raised (1, 6, 7). (DZ) twins, aged 17-65 yr, were recruited through local advertising and the Australian National Health and Medical Research Council Twin Registry. Subjects were screened to exclude any pairs in which one or both twins had renal or liver impairment or a history of myocardial infarction, or was receiving drug treatment for chronic diseases. Nine individuals were receiving current treatment with nonsteroidal antiin- flammatory drugs. The zygosity of each twin pair was assessed by questionnaire, admin- istered independently to each twin (11). DNA fingerprinting (12) in a subset of 42 same-sex pairs found one pair classified as DZ by the questionnaire to be MZ, indicating a likely error rate of 2.4%. The misclassified pair was reclassified before any genetic analysis. Study design It is well established that both genetic and environmental factors contribute to the variability in BP (8-10). By evalu- ating the relative contributions of genetic and environmental influences to the variability in basal plasma catecholamine levels in normotensive twins, we hoped to add further insight to the possible role of the sympathetic nervous system in normal BP control and the early development of essential hypertension. The protocol has been previously described (10). Briefly, both mem- bers of a twin pair attended on the same day, on two occasions, 7 days apart. For both visits, pairs were seen between 0700-1000 h after fasting overnight. At the first visit, written informed consent was obtained from all participants before further involvement. The zygosity questionnaire and a health and lifestyle questionnaire (13) were administered to each twin independently. Subjects were supine, and a scalp vein needle was inserted into a forearm vein for blood sampling. After flushing with Na heparin, the subjects were left to he quietly for 20 min in a room maintained at 21 C. After discarding the first milliliter, blood was sampled into iced tubes containing EGTA and glutathione and imme- diately centrifuged at 4 C, and the plasma was stored at -80 C until analysis. Subjects and Methods Subjects The recruitment and zygosity of the subjects have been described previously (10). Briefly, 109 pairs of monozygous (MZ) and dizygous At the second visit, weight and height were measured. Body mass index (BMI) was calculated by dividing weight (kilograms) by height (meters) squared. After 5 min of rest, supine BP was measured every 2 min for 20 min by the Diiamap 845XT (Critikon, Inc., Tampa, FL). The flit reading was discarded, and systolic and diastolic BPS were regarded as the mean of the remaining 10 values. A 24-h urine sample was collected for determination of urinary sodium excretion. Received September 8, 1992. Accepted May 4, 1993. The dissociation of our venepuncture and BP measures was designed Address all correspondence and requests for reprints to: Dr. P. D. to reduce, as far as possible, the potential influence that any anxiety Williams, University Department of Medicine, Box X2213, GPO Perth, associated with the venepuncture procedure may have had on BP 6001 Western Australia, Australia. measurement. In addition, we measured both BP and catecholatie 794