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Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression

  1. Author:
    Hendrickson, S. L.
    Lautenberger, J. A.
    Chinn, L. W.
    Malasky, M.
    Sezgin, E.
    Kingsley, L. A.
    Goedert, J. J.
    Kirk, G. D.
    Gomperts, E. D.
    Buchbinder, S. P.
    Troyer, J. L.
    O'Brien, S. J.

  2. Author Address

    [Hendrickson, Sher L.; Lautenberger, James A.; Chinn, Leslie Wei; Sezgin, Efe; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Malasky, Michael; Troyer, Jennifer L.] SAIC Frederick Inc, Lab Genom Divers, Frederick, MD USA. [Kingsley, Lawrence A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Kingsley, Lawrence A.] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA USA. [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA. [Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gomperts, Edward D.] Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. [Buchbinder, Susan P.] San Francisco City Clin, Dept Publ Hlth, San Francisco, CA USA.;Hendrickson, SL, NCI, Lab Genom Divers, Frederick, MD 21701 USA.;hendricksons@mail.nih.gov
    1. Year: 2010
    2. Date: Sep
  2. Journal: Plos One
    1. 5
    2. 9
    3. Pages: 8
  4. Type of Article: Article
  5. Article Number: e12862
  6. ISSN: 1932-6203
  1. Abstract:

    Background: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression. Methodology/Principal Findings: Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 European American patients from five US AIDS cohorts. Successfully genotyped SNPs gave 50% or better haplotype coverage for 679 of known NEMP genes. With a Bonferroni adjustment for the number of genes and tests examined, multiple SNPs within two NEMP genes showed significant association with AIDS progression: acyl-CoA synthetase medium-chain family member 4 (ACSM4) on chromosome 12 and peroxisomal D3, D2-enoyl-CoA isomerase (PECI) on chromosome 6. Conclusions: Our previous studies on mitochondrial DNA showed that European haplogroups with presumed functional differences were associated with AIDS progression and HAART mediated adverse events. The modest influences of nuclear-encoded mitochondrial genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS pathogenesis.

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External Sources

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  2. DOI: 10.1371/journal.pone.0012862
  3. View record in Web of Science®
  4. WOS: 000282002900012

Library Notes

  1. Fiscal Year: FY2009-2010
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