Table (from New
Scientist 14/11/98, p.35) giving examples of how drugs very in their
effectiveness, in accordance with the variation of a particular gene.
Gene. |
Disease. |
Treatment. |
Response. |
Serotonin
receptor subtype 5-HT2A. |
Schizophrenia. |
Clozapine. |
People with
two copies of the C102 form of this gene are less likely to respond to
clozapine. |
Apolipoprotein
E (ApoE). |
Alzheimer’s
disease. |
Tacrine. |
The ApoE4 form
of this gene is associated with an increased risk of Alzheimer’s and a poor
response to tacrine. |
CYP2D6-part of
the cytochrome P450 gene family. |
Depression. |
Desipramine
and other drugs. |
People with a
CYP2D6 defect tend to metabolise drugs slowly, and may be poisoned by the
accumulation of toxic drugs. |
N-acetyltransferase. |
Heart attack. |
Procainamide
(anti-arrhythmic drug). |
Procainamide
can lead to fatal liver infections in slow acetylators |
Genes, have a considerable influence
over how someone reacts to a drug. This is because genes play a central role in
protein synthesis. The primary protein that forms then twists and internally
bonds to form a tertiary protein or an enzyme. Thus it is these enzymes that
vary as a result of inheriting different versions of a gene, i.e. the enzymes
differ in how they metabolise, absorb and excrete drugs.
Rsearchers have identified several dozen enzymes that vary in
their activity throughout the population and that probably dictate people’s
response to drugs. To understand these differences researchers are specifically
looking at SNPs (Single Nucleotide Polymorphisms). SNPs are variants in genes
that make us an individual, i.e.:
99.9% genes are identical but 3 million SNPs, that occur about once every thousand
bases accounts for the remaining 0.1%.
Thus, SNPs distinguish those who can
benefit from a particular drug from those who cannot.