Division of Molecular Biology & Human Genetics
Tuberculosis Host Genetics
medicine it is well known that few medications are equally effective in
all patients. Individuals vary in their response to the same
medication, and often their response is an adverse reaction to the
medication which can become life-threatening. Pharmacogenetics studies
the genetic basis for this inter-individual variation and how it
determines the individual's response to medication. This research field
therefore plays a decisive role in improving the safety and efficacy of
drug treatments. The aim of Pharmacogenetics is therefore, to develop
“personalised” medical treatments, or the”right medication, for the
right patient, at the right dose”.
N-acetyltransferases (NAT) are one of the earliest drug-metabolising
enzymes (DMEs) studied that exhibited a variation in the N-acetylation
of drugs in the liver. The NATs are responsible for the inactivation of a
number important therapeutics, including para-amino-salicylate (PAS),
and isoniazid (INH), used in the treatment of tuberculosis (TB).
Specific variants of the NAT genes are possessed by different
individuals and/or populations, and subsequently, these variants can
impair the efficacy of the anti-TB drug treatment regimens via the
altered metabolism of these drugs. Several of these genetic variations
that cause the altered enzyme activities, have been well characterised,
particularly in the case of the NAT2 enzyme, which inactivates INH.
However, there are numerous others, in both NAT enzymes, whose effect on
the metabolism of drugs such as PAS, is as yet unknown. Currently our
research group is investigating the factors contributing to the very
high incidence of TB in a population of Cape Town, and a significant
part of our research focusses on elucidating the contribution of the NAT
enzymes to the high incidence of TB peculiar to this population.