Mitochondrial genes

In addition to genes found within the nucleus, some polymorphic versions of mitochondrial genes have been linked to the incidence of HIV drug side-effects. For example, a group of polymorphisms called haplogroup T (comprising C7028T, G10398A and G13368A) has been associated with a fivefold elevated risk of peripheral neuropathy in patients taking ddI (didanosine, Epivir) or d4T (stavudine, Zerit).1 This polymorphism is particularly common in European populations, but its role in other races is yet to be determined.

It is unclear why this haplotype causes an increase in the incidence of neuropathy as it is not associated with any known disease or disruption in mitochondrial function. However, researchers have hypothesised that it makes mitochondria more susceptible to the toxic effects of nucleoside analogues, possibly through effects on DNA polymerase gamma.

References

  1. Hulgan T et al. Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an Adult Clinical Trials Group study. AIDS 19: 1341-1349, 2005
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

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