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.