Mitochondrial Haplogroups Are Associated With Risk of Neuroretinal Disorder in HIV-Positive Patients

Author:

Hendrickson, S. L.

Jabs, D. A.

Van Natta, M.

Lewis, R. A.

Wallace, D. C.

O'Brien, S. J.
Author Address

[Hendrickson, Sher L.; O'Brien, Stephen J.] Natl Canc Inst, Lab Genom Divers, Ft Detrick, MD 21702 USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Jabs, Douglas A.; Van Natta, Mark] Johns Hopkins Univ, Dept Epidemiol, Ctr Clin Trials, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Lewis, Richard Alan] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. [Lewis, Richard Alan] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Lewis, Richard Alan] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lewis, Richard Alan] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Wallace, Douglas C.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92717 USA. [Wallace, Douglas C.] Univ Calif Irvine, Dept Biol Chem, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92717 USA. [Wallace, Douglas C.] Univ Calif Irvine, Dept Pediat, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92717 USA.;Hendrickson, SL, Natl Canc Inst, Lab Genom Divers, Ft Detrick, MD 21702 USA.;hendricksons@mail.nih.gov

Abstract:

Although highly active antiretroviral therapy has improved survivorship dramatically and decreased the incidence of cytomegalovirus retinitis among patients with AIDS, other ophthalmic complications continue to occur. One complication observed in similar to 12% of HIV-infected patients is a presumed neuroretinal disorder (NRD), manifested as decreased contrast sensitivity and associated with vague subjective complaints of hazy vision. Pathologically, patients with AIDS even without ocular opportunistic infections have loss of optic nerve axons, suggestive of mitochondrial dysfunction. We explored whether variation in mitochondrial DNA was associated with time to NRD in HIV-infected patients in the Longitudinal Study of Ocular Complications of AIDS cohort. Within the Western European, or "N", mitochondrial DNA macrohaplogroup, haplogroup J, was associated with 80% decrease in the risk of progression to NRD during the study (hazard ratio = 0.20, P = 0.039) and suggested an independent association with protection against NRD in a cross-section of all patients taken at enrollment (1.5% vs. 8.9% in patients with vs. without haplogroup J, respectively, P = 0.05). These data suggest that mitochondrial genotype may influence propensity to develop HIV-associated NRD in patients with AIDS.

See More

Author Address