Potential Role Of Genetic Factors Research Articles

Potential biological markers in individuals at high risk for developing alcoholism.

N THE PAST two decades a plethora of scientific I evidence has been accumulated to support the notion that alcoholism is a familial disorder with the presence of genetic factors. It is now well established that sons of alcoholic fathers are approximately four times more likely to develop alcoholism compared to the male offspring of nonalcoholics.’ Indeed, the evidence supporting the contribution of genetic factors in alcoholism is sufficiently compelling to warrant a search for markers of the genetic influence. It should be noted that the antecedent factors or predisposition toward alcoholism might well be assessed with the use of various strategies. It may be possible to study genetic factors by comparing abstinent alcoholics to control subjects or by comparing abstinent alcoholics with a positive family history to abstinent alcoholics with a negative family history of alcoholism. While this particular strategy may yield interesting findings, the interpretation of the data may be confounded by significant differences in drinking history, differential age of onset of alcohol abuse, as well as numerous other clinical variables such as number and severity of withdrawal episodes, alcohol-related medical complications, etc. A strategy typically used in the study of genetically determined disorders is the use of large family pedigrees. This powerful approach enables the investigator to study large families with alcoholism, and compare them to control families where alcoholism is absent. This particular strategy is most compelling if one studies genetically determined diseases such as Huntington’s disease where the phenotypic expression is easily characterized and specific phenotypic markers are readily available. This ap proach is indeed most powerful to examine the pattern of inheritance. However this method is most difficult to implement without the availability of valid and reliable biological or behavioral markers. In the last few years investigators concerned with the potential role of genetic factors in alcoholism have used the high risk paradigm. Comparing the sons of alcoholic fathers and nonalcoholic fathers is a useful approach for examining potential biologid or behavioral factors associated with a predisposition for alcoholism. This particular strategy has been utilized in biological as well as behavioral investigations, and has already yielded promising data fiom various studies. EEG

Genetic differences in mechanisms involving neuroregulators

Publisher Summary This chapter discusses genetic differences in mechanisms involving neuroregulators. The potential role of genetic factors becomes of great importance in terms of a number of theories of the illness. The possibility of genetic variation in catecholamine synthesizing activity is suggested by several lines of evidence. In animals, strain and subline differences have been reported in the amounts of biogenic amines in brain regions of mice and rats and in the utilization and uptake of cardiac norepinephrine in mice. In humans, a variety of forms of pheochromocytoma have been shown to be associated with familial factors. There are known genetic variations in adrenocortical and adrenomedullary structure. Genetic variations in steroid hormones produced by the adrenal cortex and in thyroid hormone have been associated with behavioral changes, and further e search for genetic variation in the enzymes involved in catecholamine biosynthesis would be fruitful. The use of inbred mouse strains is particularly advantageous in studies of genetic variation and provides a powerful tool for subsequent behavioral and genetic analysis.