Analysis of heritability of hormonal responses to alcohol in twins: Beta-endorphin as a potential biomarker of genetic risk for alcoholism

Background: Hormonal responses to alcohol have been reported to differ in s ubjects with and without a family history of alcoholism which suggests that alcohol-induced hormonal changes might be used to identify individuals who are at elevated genetic risk for developing alcoholism. However, before a biological response can be used as a marker of genetic risk for disease, it must first be demonstrated that the response is, in fact, heritable. The p resent study was designed to determine whether hormonal responses to alcoho l are heritable. Methods: The adrenocorticotropic hormone (ACTH), beta-endorphin (beta-E), c ortisol (CORT), and prolactin (PRL) responses to alcohol were examined in m ale and female identical (monozygotic or MZ) and fraternal (dizygotic or DZ ) twin pails. Male subjects consumed 0.35 g ethanol/kg body weight (BW) and females consumed 0.325 g ethanol/kg BW in each of two alcohol drinking ses sions administered 1 hr apart (total dose of 0.7 g/kg BW in males and 0.65 g/kg BW in females). Plasma hormone content was analyzed in samples collect ed before (resting conditions) and at 15, 60, 75, 120, 180, and 240 min aft er onset of drinking. Hormonal responses to alcohol were examined with twin analyses using the TWINAN90 program. A separate analysis was performed for each of the four hormones. A subset of subjects from each zygosity was see n on two separate occasions to establish retest reliability. Heritability o f hormonal responses to alcohol was estimated using the intraclass correlat ion approach before and after removing the contribution of covariates that have the potential of influencing the plasma levels of these hormones. Results: Resting plasma levels of all four hormones were within the expecte d range, and the beta-E ACTH, and PRL responses to the alcohol challenge ev idenced good test-retest reliability. Of the four hormones examined, the on ly one that showed significant heritability after alcohol drinking was beta -E. Heritability estimates were not altered for any of the four hormones af ter removal of the variance contributed by covariates, such as gender and a ge. Conclusions: Taken together with other recent findings, the results suggest that the beta-E response to alcohol may represent a new biomarker that can be used to identify individuals who are at elevated genetic risk for devel oping alcoholism.