Genetic Basis Of Alcoholism Essay, Research Paper

Introduction

The focus of this paper is alcoholism. The aspects that will be examined in the following pages are the biology of alcoholism, and the genetic basis determining that alcoholism is a hereditary disease. Clarification of the phases of alcoholism as well as possible explanations of the nature of the disease will be offered. Examination of studies concerning biological markers associated with alcoholism and advanced animal testing will allow further understanding of alcoholism and related problems.

With these biological components established, it is important to further explore a study of alcoholism in different ethnic groups, countries and cultures and as it relates to gender. The role that alcoholism plays in varying cultures and the reasons behind its presence it is still largely debated. Despite all of the studies and information gathered thus far, scientists are still largely undecided as to the precise etiology of this disease because of its extremely complicated combination of physical and psychological components.

Phases of Alcoholism

Due to the complicated combination of aspects that form alcoholism researchers have defined phases that attempt to separate contributors not in matters of importance, but chronology. The first phase of alcoholic tendencies begins before birth and continues to the subject s first alcoholic experience. Here in the predromal phase, genetic factors, intra uterine factors and childhood environment all contribute to the susceptibility of a person to alcoholism. It is obvious from this point why alcoholism runs in families; genetics, intra uterine conditions and childhood environment would all be greatly influenced by an alcoholic mother. The second stage of alcoholic development is the induction phase, this is the period in which a psychological attachment to alcohol is developed through a variety of the pleasure giving aspects that alcohol may have for the subject. The next phase is physical dependence, it is characterized by withdrawal, craving, and tremors and often a complete inability to control or curb drinking (Kissin, 1972).

One postulation by researchers and theorists is that there is a distinct psychopathology associated with alcoholism that allows an otherwise non-functional individual to feel secure enough to participate in society. Partanen et. al. (1966) found correlation between emotional instability and the likelihood of developing alcohol abuse problems. Another theory suggests that alcoholism is a conflict between dependence and interdependence. This idea continues along the same lines submitting that one of the possible reasons for a lower incidence of alcoholism among females is an acceptance of dependency on their part due to societal conditioning (Kissen and Barry, 1972).

The Heredity of Alcoholism

Children of alcoholic parents have been found to be 3 to 5 times more likely to themselves become alcoholics (Steen, 1996). This number is influenced by many factors independent of heredity, however the genetic basis for alcoholism is widely believed and studied in hopes of finding a concrete example to better understand and treat the disease. It has been estimated that genetics account for 50- 60 % of the risk for alcoholism (Roebuck and Kessler, 1972).

One significant way that the genetic basis for alcoholism has been demonstrated is with twin studies. One of the twin studies examined here took place in Finland in 1966 to determine the inheritance of the tendency to use alcoholic beverages. The Finland study consisted only of male twins; both monozygotic and dizygotic pairs were used. These twins had been raised together in most cases and therefore the information given must be considered as having been influenced by environment. The study determined a considerable degree of heritablility in the areas of density and amount of alcohol consumed but saw little correlation in the fields of lack of control or social complications arising from alcohol use (Partanen, et. al., 1966). These findings suggest that while a propensity for alcoholism is inherited in many cases, the degree to which it affects the life of an individual remains unaffected by biology.

A later twin study, conducted in Sweden and reported in 1987 also studied only male pairs but in this case the twins were adopted into non-relative families at a young age. This split-twin study allowed researchers to determine to a greater extent the importance of environmental exposure in regards to alcoholism. In this study it was found that children who had no history of alcoholism in their biological backgrounds were in relatively little danger of becoming alcoholic. This remained true whether or not they were raised in alcoholic environments. The environment did not hold much influence on the other side of the spectrum either, as children from alcoholic biological origins tended to become alcoholics as well regardless of their adoptive homes (Steen, 1996). Taking into account the inherent problems of twin studies these results are nonetheless highly suggestive of a very strong correlation between heredity and alcoholism.

Biological Markers

Efforts have been made to find a biological or genetic marker that will indicate a person s increased chances for becoming an alcoholic. Color blindness, ABO blood groups, C3 and Ss systems and taste sensitivity to phenylthiocarbamide have all been examined as possible markers but were determined to be ineffective. Color blindness is related but turns out to be often caused by liver damage resulting from heavy drinking.

A report that may have merit to it suggests a linkage of alcoholism and non-secretion of ABH blood group substances in saliva (Gurling and Murray, 1980). Different studies have found conflicting results with attempts to identify other biological markers. One researcher found a high incidence of alcoholism in blood group A in Pueblo, Colorado. Other researchers did not achieve similar results when replicating the study in Finland (Goodwin and Guze, 1972).

With more promising results, neurotransmitter-related enzymes such as dopamine beta-hydroxylase and monoamine oxidase have been linked to alcoholic tendencies. These enzymes have been found to possibly affect the health and psychological consequences of drinking as well (Murray and Gurling, 1980). Mentioned later, aldehyde dehydrogenase genes also play a significant part in incidences of alcoholism.

Women and Alcohol

Many of the studies evidenced in this paper deal exclusively with male subjects, this is due in large part to the fact that men seem to be at a greater risk for alcoholism than women are. The idea that women are less likely to become alcoholics is supported by some, but dismissed by others as the fact that perhaps no one has been asking the right questions regarding women and alcohol. However, there have been tests exclusively designed to gauge the relationship between women and alcoholism. Female alcoholics differ from male alcoholics in several ways that often seem to explain why the issue was largely neglected for decades. Women generally become alcoholics later in life when the addiction is easier to conceal. Women often experience psychological or emotional problems in conjunction with alcoholism, masking the specific issue of drinking. Alcoholism is hereditary in women as well, but apparently to a lesser extent (Goodwin, 1981). It has been reported that among heavy drinkers in the United States men outnumber women 4 to 1 (Roebuck and Kessler, 1972), but it is notable that men are more likely than women to drink in public while women may stay out of sight, possibly skewing results.

This trend of males being heavier drinkers than females continues in other countries and cultures as well. In Native American populations an alcohol related diagnosis from Indian Health Services hospitals was more than twice as likely for a man than for a woman. 26.5 % of deaths for Native American males and 13.2 % for females were alcohol related in 1995 (Beauvais, 1998). These figures may indicate that alcoholic males are more likely to incur injuries or death as a result of alcohol. In areas where culture and religion combine women may be completely abstinent, as in a 1983 study in India (Bennett et. al. 1998).

Cross Cultural Comparison

While a first glance at alcoholism and oft-enforced stereotypes would indicate that certain populations are more genetically disposed to alcohol problems, research shows otherwise. In a comparison of several vastly different populations spanning a variety of ethnic makeups there is little evidence to conclude that some groups have an increased genetic tendency towards alcoholism (Bennett et. al., 1998). Commonly held conceptions that Irish, Russian or Native American populations are biologically more susceptible to alcoholism have no foundation. One exception, the interesting example of many Asian peoples reaction to alcohol, will be discussed further in the paper.

One study by Doctors Bennett, Campillo, Chandrashekar and Gureje took as examples India, Mexico and Nigeria for a cross-cultural analysis of drinking behaviors and patterns. These particular countries were chosen because in domains such as culture, geographic location, language and ethnicity they had little in common. The goal of the researchers was to establish some type of pattern unifying drinking and drinking problems across cultural boundaries. Also, as research on drinking tends to evaluate ethnic groups in a way that can be construed as racist, such as concentrating on Hispanics, Native Americans and African Americans as compared to Whites in the United States, the researchers here emphasized the separation of these particular nations.

All three nations evaluated have histories of alcohol use in their cultures for a number of reasons. The variety of alcohol consumed in the three nations and the traditions and patterns that accompany consumption are very different. As is to be expected the problems and the extent of difficulties that these countries face to in respect to alcohol dependency are wide ranging as well. India has the least amount of problems concerning alcoholism; religion, culture and former governmental control have curbed the dangers arising from alcohol dependency. 3 % of adults in India are considered alcohol dependent, as compared to between 10 and 31 % in the United States (Bennett et. al., 1998; Steen, 1996).

Mexico, by comparison, has a much greater problem concerning alcohol dependency and consequences of drunkenness. Ranging from death from alcohol related illnesses to domestic violence to loss of productivity Mexico suffers from the most common alcohol related problems. Treatment and prevention have been instituted but some argue that the machismo culture is largely to blame (Bennett et. al., 1998).

Nigeria also has problems with alcohol abuse. Those citizens of Nigeria that are not Muslim tend to use alcohol daily as part of ceremony and quotidian activities. Drinking is generally considered less disruptive to daily life in Nigeria but heavy drinking is not looked upon favorably (Bennett et. al., 1998). These three examples demonstrate not only that drinking and alcohol abuse vary greatly from one country to another, but also that the perception of what constitutes a problem or dependency is also subject to cultural norms and values.

Although there are significant differences in the ways that people of various cultures use alcohol, and the extent to which they do so, these differences are primarily cultural. In some cases, especially in the United States, higher alcohol consumption or alcoholic tendencies are a result of acculturation. The need of a certain ethnic group to fit in with mainstream American society or deal with immigration stressors is an indication of why some groups within the same society have more binge drinkers or alcoholics than others (Makimoto, 1998). This acculturation model may account for the fact that there have been higher measured incidences of alcoholism among Irish-Americans than native Irish and Italian-Americans than among native Italians (Barry, 1972). The constantly changing atmosphere of drinking in the United States may have a magnifying effect on the habits of subsections of its citizens (Beauvais, 1998; Makimoto, 1998). For example, the fact that Pacific Islander students born in the United States may drink more than those who immigrated here may only reflect the fact that they are exposed to a part of American culture that values drinking as a social activity.

Higher rates of alcoholism in the United States are reported by ethnic minorities, giving good indication that the socio-economic status of individuals is directly related to drinking (Caetano et. al., 1998). The danger of such a statement is that it gives the impression of a homogeneous set of minorities. The truth is that within Asian Americans or Native Americans for example there is great diversity. An important aspect not to be overlooked is the wealth of differences between minorities and within minority groups that will help to determine drinking patterns. Cultural and religious aspects, as well as the history and availability of alcohol all shed light on the variance of alcohol use by different peoples, despite the fact that those people may share a same nationality (Caetano et. al., 1998).

One of the groups in the United States and Canada that appears to be most at risk for dangerous behavior related to drinking is Native Americans. Even while taking into account the great variations within the category of Native Americans, problems related to alcoholism within that ethnic group are particularly high. Historical context may have contributed as Native Americans were introduced to alcohol by a particularly hard drinking contingent of people. Settlers, trappers and pioneers all used alcohol in their dealings with Native Americans and tended to drink heavily. American Indians, having little experience with alcohol prior to the arrival of Europeans took this as their model for social drinking (Beauvais, 1998). As genetics has been shown to contribute to at least half of a predisposition to alcohol, this onset of heavy drinking as a culture may have influenced future generations.

Another aspect of the problem drinking seen on reservations and in indigenous Americans elsewhere are the fact that when they drink, Native Americans tend to drink a great deal, putting them at risk for accidents and incidents further depleting their quality of life. The loss of culture and a sense of degradation and injustice may present a feeling of hopelessness that breeds destructive behavior. Also, the tendency for American Indians to believe themselves to be more prone to alcoholism has been noted as contributing to this problem, illustrating the psychological causes for alcoholism (Beauvais, 1998).

Studies relating to African-Americans and the reasons for alcoholism among that group have similarities to those involving Native Americans. Both groups have reason to feel disenfranchised in United States culture. As is the case with Native Americans, those that do drink tend to do so heavily at a greater risk to themselves and others. Despite having a relatively low socio-economic status, African Americans report lower rates of alcohol use than Whites. Mortality rates from alcohol related illnesses and incidents are higher for African-Americans than for Whites despite lower drinking rates and equal occurrences of heavy drinking (Jones-Webb, 1998).

Asian Americans and Pacific Islanders tend to have a much lower rate of alcoholism and alcohol abuse than any other category of Americans. Again this can be attributed to a variety of reasons. The Asian American designation covers a broad range of backgrounds and ethnicities but from adolescence on Asian Americans in general have the lowest reported probability of alcohol related problems. Some factors influencing these numbers may be the tendency in Asian cultures to keep such matters private, and the fact that the economic status and high educational level attained by many Asian Americans is correlated with low alcohol abuse. The fact that many Asian Americans also live in communities with people and immigrants of the same background may reduce the acculturation aspects of increased alcohol use and abuse (Makimoto, 1998). On a different note, Asian Americans and Pacific Islanders are a particularly interesting study in this arena because they are the only ethnic group that has been found to have a proven genetic trait that may account for their comparatively low levels of alcohol consumption (Makimoto, 1998; Thomasson, and Li, 1993).

Genetic Aspects of Alcoholic Tendencies

Alcohol is broken down by the body in a catabolic process requiring two enzymes. The enzymes are called alcohol dehydrogenase and aldehyde dehydrogenase (ALDH). The first enzyme changes alcohol to acetaldehyde and the second enzyme converts that acetaldehyde to acetate. If the second enzyme, ALDH does not adequately perform its role of transforming the acetaldehyde to acetate the body responds with a series of uncomfortable reactions. These reactions include flushing; a reddening of the face and torso which is caused by an increase of blood flow to the skin. Sometimes with the flushing comes rapid heartbeat, headache, nausea, drowsiness and hypertension (Makimoto, 1998; Thomasson and Li, 1993).

This reaction is not common to all people and is most often found in people of Asian descent. The reason for this selection for Asian people is not concrete but its cause is known:

Several genes code for the ALDH enzyme, including the ALDH2 gene. Two variants of the ALDH2 gene exist. The ALDH2*1 variant produces a functional enzyme, whereas the ALDH2*2 produces an inactive enzyme. Each person inherits two copies of the ALDH2 gene, one from the father and one from the mother. People who inherit two copies of the ALDH2*2 or one copy of the ALDH2*1 gene and one copy of the ALDH2*2 gene produce an impaired ALDH enzyme and are susceptible to the flushing reaction. Because they experience the unpleasant flushing reaction, these people may consume less or no alcohol and therefore be at reduced risk for alcoholism. (Makimoto, 1998)

The reason that Asian populations have a higher occurrence of flushing and other unpleasant side effects is that the inactive gene ALDH2*2 is more commonly found in people of Asian descent. Although Asians are not the only ethnic group to have one or more of the ALDH2*2 gene they are up to 50% more likely to have it than Caucasians. It follows that in order to avoid the unpleasant effects of flushing Asians would be more likely to abstain from drinking or to drink less. This can be seen as a protection against alcoholism that is found predominantly in Asian populations.

An interesting aspect of the incidence of alcoholism found in populations where flushing is prevalent is that of those alcoholics found, all of them were heterozygous. In a test of 50 Chinese alcoholics in Taipei 12% had the ALDH2*2 allele. The fact that none of them had 2 ALDH2*2 alleles leads researchers to believe that possessors of homozygous ALDH2*2 alleles have such a strong flushing reaction that they are prevented from becoming alcoholic. It is apparent that the ALDH2*2 allele is instrumental in preventing alcoholism in Asian cultures (Thomasson and Li, 1993). What remains a mystery is why Asian populations are apparently the only ones to benefit from the selection for the ALDH2*2 allele.

Another allele thought to contribute to the prevalence of alcoholism is called the A1 allele. The A1 allele is associated with the dopamine receptor. Due to the fact that alcohol is a drug that affects dopamine levels it was believed that the A1 allele could hold a key to discovering the genetic reasons for alcoholism. The A1 allele has also been linked to a variety of mental disorders. Since the initial study connecting alcoholism to the A1 allele, it has not been replicated and there is no new evidence to prove that the two are connected. In fact the theory that the A1 allele is related to either mental illness or alcoholism has been refuted but it remains a variable when examining brains of people of different ethnic backgrounds. Although genetic differences regarding the A1 allele have not been found in relation to higher alcoholism levels among certain populations it is interesting to note that the A1 allele frequency is less than 10% in Yemenite Jews, is about 40% in American Blacks, and is about 80% in Cheyenne Indians. (Steen, 1996 p. 213) Given that these frequencies mirror the occurrence of alcoholism in the stated populations one wonders if the A1 allele is significant in some way.

Animal Studies and Technology

For a wide variety of reasons, animal studies cannot be relied upon to explain human behavior. It is entirely possible though, to look at animal studies to try and gain insight into some of the reasons that humans are afflicted in certain ways. Some of the best evidence illustrating a genetic factor in alcoholism has been achieved through the inbreeding of lab animals. The heredity of alcoholism has been better explained by inbreeding mice and rats to determine whether offspring would have the same alcoholic preferences as parents. With this selective breeding, strains of mice and rats did develop family influenced preferences to alcohol, but even with a line of rats developed through 37 generations it was impossible for researchers to obtain pure lines of alcoholic and abstaining rats. This led researchers to determine that alcoholism is a disease influenced by more than one gene loci (Goodwin and Guze, 1972). Science has advanced phenomenally since this data was collected and it is important to note that this discovery opened many doors.

The establishment that the heredity of alcoholism is polygenic has revealed other theories that attempt to explain the genetic differences in offspring from the same pair of mice. Animals that prefer alcohol to water when given the chance tend to have a greater tolerance for alcohol. They have higher alcohol dehydrogenase and aldehyde dehydrogenase activity, reducing acetaldehyde levels as compared to low preference animals. All of the data concerning certain mice and rats preference for alcohol over water is relative to the fact that their metabolic processes enable them to process alcohol at a more efficient rate (Goodwin and Guze, 1972). This can be compared to humans in many ways, one of them being that studies have found that people able to tolerate large amounts of alcohol without much exposure are often prone to become alcoholics later in life (Goodwin, 1981).

Another notable aspect of early tests conducted on rodents to determine an inclination for alcoholism dealt with malnourished rats seeking alcohol rather than water. Rats and mice experiencing vitamin-deficiency drank more alcohol than healthy rats did. It was hypothesized that rats recognized the higher caloric value of alcohol and consumed it as a matter of survival. In looking for the adaptive significance of alcoholism this example is promising. Researchers however declare this correlation as irrelevant. It is stated that the actions of a rat seeking caloric value from alcohol cannot be basis for human alcoholism (Goodwin and Guze, 1972).

Animal testing has reached new domains since the publication of Goodwin and Guze. Gene knockout technology and transgenic animals have been instituted and are helping to create better test subjects from genetically engineered lab animals. Gene knockout technology renders a gene in an animal mute and extra genes are added to transgenic animals to form desired combinations. These methods are particularly helpful because they are able to isolate the function of a specific gene and determine whether it is pertinent to the study at hand (Homanics and Hiller-Sturmhofel, 1997).

In the specific area of testing for alcoholism the most common method of using the knockout technology is to interrupt receptors of seratonin for example, thereby learning of the significance that seratonin has in the brain of an alcoholic. In one test it was learned that some of alcohol s effects are due to a particular receptor but aspects such as tolerance and withdrawal are not. These learnings will have particular significance in the future of medical treatment for alcoholism. As alcohol dependency has been determined to be polygenic, the benefits of knockout technology are harder to ascertain as disrupting one gene will have unforeseen consequences on others. However, new technology is continually being developed to overcome these roadblocks (Homanics and Hiller-Sturmhofel, 1997).

Conclusion

It has been demonstrated in the preceding pages that alcoholism has many facets. Despite amazing 21st century technology, centuries of consumption and decades of dedicated research alcoholism still remains one of the most difficult diseases to fully understand. The combination of environment and biology makes alcoholism and alcohol related diseases particularly interesting to study. The difficulties involved in establishing good data are many because of the inseparable relationship of alcoholism s contributors. Through the countless studies that have been performed alcoholism has been demystified to a large extent. Thanks to the removal of some of the social stigma attached to alcoholism, and the scientific advances that have been made, better treatment is now available.

References Cited

Journals:

Beauvais, F. (1998) American Indians and Alcohol. Alcohol Health & Research World 22: 253-259.

Bennet, L., Campillo, C., Chandrashekar, C., Gureje, O. (1998) Alcoholic Beverage Consumption in India, Mexico, and Nigeria: A Cross-Cultural Comparison. Alcohol Health & Research World 22: 243-252.

Caetano, R., Clark, C.L., Tam, T. (1998) Alcohol Consumption Among Racial/Ethnic Minorities. Alcohol Health & Research World 22: 233-241.

Homanics, G., Hiller-Sturmhofel, S. (1997) New Genetic Technologies in Alcohol Research. Alcohol Health & Research World 21: 298-309.

Jones-Webb, R. (1998) Drinking Patterns and Problems Among African-Americans: Recent Findings. Alcohol Health & Research World 22: 260-264.

Makimoto, K. Drinking Patterns and Drinking Problems Among Asian-Americans and Pacific Islanders. Alcohol Health & Research World 22: 270-275.

Thomasson, H., Li, T. (1993) How Alcohol and Aldehyde Deydrogenase Genes Modify Alcohol Drinking, Alcohol Flushing and the Risk for Alcoholism. Alcohol Health & Research World 17: 167-173.

Books:

Barry, H. (1972) Psychological factors in Alcoholism. In B. Kissen and H. Begleiter (ed.) The Biology of Alcoholism, vol. 3. New York: Plenum Press.

Goodwin, D. W. (1981) Alcoholism: The Facts. Oxford: Oxford University Press.

Goodwin, D. W. and Guze, S.B. (1972) Heredity and Alcoholism.

Kissen, B. (1972) The Pharmacodynamics and Natural History of Alcoholism. In B. Kissen and H. Begleiter (ed.) The Biology of Alcoholism, vol. 3. New York: Plenum Press.

Murray, R. M. and Gurling H. (1980) Genetic Contributions to Normal and Abnormal Drinking. In M. Sandler (ed.) Psychopharmacology of Alcohol. New York, Raven Press.

Partanen, J., Bruun, K. and Markkanen, T. (1966) Inheritance of Drinking Behavior: A study of Intelligence, Personality and use of Alcohol of Adult Twins. New Brunswick, Rutgers University Center of Alcohol Studies.

Roebuck, J B. and Kessler, R. G. (1972) The Etiology of Alcoholism. Springfield: Charles C. Thomas.

Steen, R.G. (1996) DNA & Destiny: Nature & Nurture in Human Behavior. New York: Plenum Press.