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Genetics of Serum Dehydroepiandrosterone Sulfate and Its Relationship to Insulin in a Population-Based Cohort of Twin Subjects

Division of Endocrinology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University (J.E.N., T.Y.W.), Richmond, Virginia 23398; Department of Biochemistry, Royal Prince Alfred Hospital (J.B.W.), Sydney 2050, Australia; Queensland Institute of Medical Research (J.B.W., G.Z., J.C., K.M.K., G.W.M., N.G.M.) and Department of Psychiatry (K.M.K.), University of Queensland, Brisbane 4029, Australia; and Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine (A.C.H.), St. Louis, Missouri 63108

Address all correspondence and requests for reprints to: John E. Nestler, M.D., Medical College of Virginia, P.O. Box 980111, Richmond, Virginia 23298-0111. E-mail: nestler{at}hsc.vcu.edu

Abstract

Previous studies have shown a significant effect of insulin administration on serum dehydroepiandrosterone sulfate (DHEA-S) concentration and its metabolic rate, with evidence for the effect in men, but not in women. This could lead to differences in the sources of variation in serum DHEA-S between men and women and in its covariation with insulin concentration. This study aimed to test whether these hypotheses were supported in a sample of healthy adult twins.

Serum DHEA-S (n = 2287) and plasma insulin (n = 2436) were measured in samples from adult male and female twins recruited through the Australian Twin Registry. Models of genetic and environmental sources of variation and covariation were tested against the data.

DHEA-S showed substantial genetic effects in both men and women after adjustment for covariates, including sex, age, body mass index, and time since the last meal. There was no significant phenotypic or genetic correlation between DHEA-S and insulin in either men or women.

Despite the experimental evidence for insulin infusion producing a reduction in serum DHEA-S and some effect of meals on the observed DHEA-S concentration, there were no associations between insulin and DHEA-S at the population level. Variations in DHEA-S are due to age, sex, obesity, and substantial polygenic genetic influences.

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