31Reclassifi cation of Diseases
Because all major diseases have a genetic component, knowledge of genetic basis
helps in distinguishing between clinically similar diseases. Classifying diseases
based on genetic differences in affected individuals rather than by clinical symp-
toms alone makes diagnosis and treatment more effective. Identifying human
genetic variations will eventually allow clinicians to subclassify diseases and indi-
vidual therapies. Several diseases can now be described in molecular terms as some
defects can give rise to several disorders. Reclassifi cation of diseases on molecular
basis rather than according to symptoms and gross pathology may enable the use of
one drug to treat a number of diseases with the same molecular basis. Another way
of reclassifi cation of human diseases will be subdivision of patient populations
within the same disease group according to genetic biomarkers and response to
medications.
Many common diseases represent collections of different conditions each of
which may have its own genetic cause. Advances in the diagnosis, treatment, and
classifi cation of human disease will depend on discovery of the function of each of
the human genes. These genes will enable the sub-classifi cation of diseases based
on mechanism and clinical characteristics rather than symptoms alone. Taking into
account the thousands of genes on each of the 23 chromosomes and the prediction
that common diseases like diabetes and hypertension may be caused by three to one
hundred different genes, this exciting process may well take several years of intense
work by a global network of investigators working in universities and industry. This
knowledge will revolutionize all aspects of medicine at the level of the patient and
is relevant to the development of personalized medicine.
An example of the changing attitude towards the molecular basis of disease is the
genetic basis of migraine, anxiety, and depression. This has been applied to discov-
ery of the relevance of the dopamine receptor gene (DR D2 ) to migraine. DR D2 recep-
tors are known targets of anti-emetic drugs used in migraine, and numerous
polymorphisms have been identifi ed in the DR D2 gene. DR D2 receptor antagonists
have also been approved for the treatment of psychoses, anxiety, and depression.
There is a genetic basis of the link between migraine, depression, and anxiety. The
practical implications of this new information are the potential new indications for
the numerous compounds that modulate the dopaminergic system and that are being
developed only as neuroleptics. Clinical trials for the potentially new indications
can be optimized by genotype analysis of patients with migraine, depression, and
anxiety disorders.
Some variation in drug response may result from inadequate classifi cations of
disease. For example, although two leukemias may appear identical morphologi-
cally, they may have different molecular profi les and thus respond differently to
drug treatments. Without the molecular classifi cation, the leukemias appear identi-
cal, and variation in response to the prescribed treatments would be highly unpre-
dictable. More precise categorization of disease can potentially improve drug
treatment by specifying which patients will respond to which treatments.
Reclassifi cation of Diseases