African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy During Antiretroviral Therapy

J Infect Dis. 2010 Jun 1;201(11):1703-7. doi: 10.1086/652419.

Abstract

Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse-transcriptase inhibitors was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine whether nucleoside reverse-transcriptase inhibitor-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic black persons with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (odds ratio, 3.7 [95% confidence interval, 1.1-12.0]). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to nucleoside reverse-transcriptase inhibitor-associated toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • African Continental Ancestry Group
  • Aged
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • DNA, Mitochondrial / genetics*
  • Female
  • Gene Frequency
  • Humans
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / genetics*
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • DNA, Mitochondrial
  • Reverse Transcriptase Inhibitors

Grant support