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 subjects 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 present study was designed to determine whether hormonal responses to alcohol are heritable.


METHODS
The adrenocorticotropic hormone (ACTH), beta-endorphin (beta-E), cortisol (CORT), and prolactin (PRL) responses to alcohol were examined in male and female identical (monozygotic or MZ) and fraternal (dizygotic or DZ) twin pairs. 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 sessions 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 collected before (resting conditions) and at 15, 60, 75, 120, 180, and 240 min after 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 seen on two separate occasions to establish retest reliability. Heritability of hormonal responses to alcohol was estimated using the intraclass correlation 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 expected range, and the beta-E, ACTH, and PRL responses to the alcohol challenge evidenced good test-retest reliability. Of the four hormones examined, the only one that showed significant heritability after alcohol drinking was beta-E. Heritability estimates were not altered for any of the four hormones after removal of the variance contributed by covariates, such as gender and age.


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 developing alcoholism.
Froehlich
J C
JC
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5124, USA. jcfroehl@iupui.edu
Zink
R W
RW
Li
T K
TK
Christian
J C
JC
D000328:Adult; D000437:Alcoholism / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001944:Breath Tests; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics; D001615:beta-Endorphin / Q000097:blood / Q000187:drug effects / Q000235:genetics*
D015415:Biomarkers; D002492:Central Nervous System Depressants; D000431:Ethanol; D001615:beta-Endorphin