A genotype-controlled analysis of plasma dopamine beta-hydroxylase in healthy and alcoholic subjects: evidence for alcohol-related differences in noradrenergic function.
BACKGROUND
Norepinephrine and dopamine mediate important aspects of alcoholism and alcohol withdrawal. Dopamine-beta-hydroxylase (DbetaH) converts dopamine to norepinephrine. A recent study demonstrated a strong association between variance in plasma DbetaH activity and a novel polymorphism (DBH-1021C-->T) at the structural locus (DBH) encoding DbetaH protein.


METHODS
Our study investigated whether the DBH-1021C-->T polymorphism and plasma DbetaH activity were associated with alcoholism or with delirium tremens (DT) during alcohol withdrawal by analyzing 207 German alcoholic and 102 healthy control subjects. We also examined the influence of the polymorphism on enzyme activity.


RESULTS
Mean (+SD) plasma DbetaH activity measured in alcoholic subjects abstinent was significantly lower than that observed in control (27.7 + 16.7 vs. 35.6 + 18.8; p =.01). It did not differ between subjects with DT during withdrawal and subjects with mild withdrawal symptoms. The T allele of the DBH-1021C-->T polymorphism was significantly associated with lower plasma DbetaH activity. None of the alleles or genotypes were associated with alcoholism or DT.


CONCLUSIONS
The data indicate that the alcoholism-related reduction in plasma DbetaH activity is independent of genotype at DBH-1021C-->T and replicate the finding that DBH-1021C-->T is strongly associated with plasma DbetaH activity in a native Western European population.
Köhnke
Michael D
MD
University Hospital of Psychiatry and Psychotherapy, Tübingen University Hospital, Tübingen, Germany.
Zabetian
Cyrus P
CP
Anderson
George M
GM
Kolb
Werner
W
Gaertner
Ines
I
Buchkremer
Gerhard
G
Vonthein
Reinhard
R
Schick
Sandra
S
Lutz
Ulrich
U
Köhnke
Annette M
AM
Cubells
Joseph F
JF
D000328:Adult; D000430:Alcohol Withdrawal Delirium / Q000097:blood; D000437:Alcoholism / Q000097:blood / Q000235:genetics*; D000483:Alleles; D004299:Dopamine beta-Hydroxylase / Q000097:blood / Q000235:genetics*; D005838:Genotype; D005858:Germany; D006579:Heterozygote; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D013375:Substance Withdrawal Syndrome / Q000097:blood
D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine