Heredity studies to determine the genetic liability for alcoholism,
including studies of twins, and adoption studies have been undertaken.
Results show there appear to be two types of alcoholics: primarily
male with a 9-fold genetic risk; and both male and female with
a lesser genetic risk, but a greater significant environmental
influence leading to an earlier onset of alcoholism. It has been
proposed that the difference between the two types is related
to the inherited personalities, e.g.: easily stressed individuals
are more susceptible to alcoholism, in particular in a heavy drinking
culture. It has also been proposed that alcoholism is a polygenetic
disorder whereby different genes affect or influence the frequency
and quantity of alcohol consumed as well as the development of
neuro-adaption or tolerance by an individual.
Indeed, studies in anima l models and humans have identified both
genetic and environmental factors contributing to alcohol consumption,
such that this complex behavioural trait is influenced by multiple
factors: Genetic factors specifically related to the pharmacology
of alcohol; Psychological factors and Socio-cultural factors.
There are two primary biological or genetic factors that influence
alcohol consumption behaviour and the development of alcoholism:
alcohol metabolism and neuro-adaption. In the US population, for
example, there is a three-fold variation in the rate of alcohol
metabolism and hence elimination of alcohol from the body, which
determines the level and duration of exposure of the body organs
to alcohol. Of this variation, approximately 4060% is directly
attributable to genetics and the remainder to environmental influences
(concurrent consumption of food and/or other drugs).
An increased rate of alcohol metabolism confers a lower blood
alcohol and/or acetaldehyde concentration and less toxicity to
tissues and organs, while a decreased rate confers a higher concentration
that can infer systemic cardiovascular and gastrointestinal adverse
reactions, such as nausea, headache, tachycardia, low blood pressure
and facial flushing. Alcohol is metabolised primarily by the enzyme
alcohol dehydrogenase (ADH) to acetaldehyde. Acetaldehyde is further
metabolised by the enzyme acetaldehyde de hydrogenase (AlDH) to
acetate. There are genetic variants of ADH and AlDH, which are
more or less active at metabolising. Less activity results in
an inability to metabolise alcohol or acetaldehyde and a high
blood alcohol or acetaldehyde concentration results and remains
until the secondary metabolic pathway is induced.
Asian populations, (Chinese and Japanese) inherit primarily the
active ADH2 variant whereby alcohol is rapidly converted to acetaldehyde,
but they also primarily inherit the inactive AlDH22 gene whereby
the toxic acetaldehyde is not converted to acetate, so it accumulates
in the blood. A systemic adverse reaction ensues that generally
discourages excessive consumption and effectively protects these
individuals against the development of alcoholism. The protection
is relative rather than absolute, as the adverse effects can be
overcome with a slowed drinking pattern.
Tolerance to the adverse behaviourally-impairing effects of ethanol
on the central nervous system and on motor function develops with
chronic or repeated drinking enabling heavier consumption; the
adverse effects generally discourage excessive consumption. Continued
excessive consumption can be encouraged by a relative insensitivity,
also genetically predisposed, to the adverse systemic cardiovascular
and gastrointestinal effects of a high blood concentration of
alcohol and acetaldehyde, and to those of the central nervous
system and motor function.
The psychological factors include an expectancy of pleasurable
effects such as social stimulation, that is, positive effects
which occur at a low to moderate level of alcohol consumption.
Conversely, expectancy of adverse effects (loss of central nervous
system and motor skills) are negative reinforcing effects which
occur at higher levels of alcohol consumption and which generally
discourage excessive consumption.
The socio-cultural factors contributing to consumption behaviour
include ethnicity, family, peers and religion. Thus some people
drink alcohol but others do not, some people drink more alcohol
than others and some people drink alcohol despite negative consequences.
These differences in alcohol consumption behaviour reflect the
fact that they experience different kinds of environmental conditions
as well as different genetic profiles.
Continued excessive alcohol consumption leads to alcoholism. Physical
dependence is exemplified by a series of systemic and behavioural
symptoms upon withdrawal of alcohol, primarily mediated by autonomic
nervous system hyper-activity. Psychological dependence is exemplified
by craving or impaired control leading to a loss of control in
consumption and a relapse in behaviour.
The rate of alcoholism is 5x higher in families of alcoholics
than in the general population, which is currently the best predictor
of the development of alcoholism for an individual. If the influence
of family environment is removed, the rate of alcoholism is still
3x higher in the adopted children of alcoholics than those of
non-alcoholics, whereby a low level of response to alcohol at
age 20 years was associated with a four-fold greater likelihood
of developing alcoholism.
An unanswerable ethical or moral dilemma often raised now, is
that not all individuals with a genetic predisposition will develop
alcohol problems and as such, positive identification may result
in an unfair restriction of employment opportunities, and that
of automobile and health insurance.
Creina Stockley is Health and Regulatory Manager at the Australian
Wine Research Institute and a member of The AIM Editorial Board.