eprintid: 13552 rev_number: 19 userid: 677 importid: 512 dir: disk0/00/01/35/52 datestamp: 2012-08-21 14:16:45 lastmod: 2019-02-02 15:55:19 status_changed: 2012-08-21 14:16:45 type: article metadata_visibility: show contact_email: hendricksons@mail.nih.gov item_issues_count: 0 eprint_status: archive creators_name: Hendrickson, SL creators_name: Lautenberger, JA creators_name: Chinn, LW creators_name: Malasky, M creators_name: Sezgin, E creators_name: Kingsley, LA creators_name: Goedert, JJ creators_name: Kirk, GD creators_name: Gomperts, ED creators_name: Buchbinder, SP creators_name: Troyer, JL creators_name: O'Brien, SJ creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: kingsley@pitt.edu creators_email: creators_email: creators_email: creators_email: creators_email: creators_email: creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: KINGSLEY creators_id: creators_id: creators_id: creators_id: creators_id: creators_id: contributors_type: http://www.loc.gov/loc.terms/relators/EDT contributors_name: Badger, Jonathan H. title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression ispublished: pub divisions: sch_gsph_epidemiology divisions: sch_gsph_infectiousdiseasesmicrobiology full_text_status: public 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 nuclearencoded mitochondrial genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS pathogenesis. date: 2010-10-29 date_type: published publication: PLoS ONE volume: 5 number: 9 pagerange: 1 - 8 refereed: TRUE id_number: 10.1371/journal.pone.0012862 other_id: NLM PMC2943476 pmcid: PMC2943476 pmid: 20877624 mesh_headings: Acquired Immunodeficiency Syndrome--genetics mesh_headings: Acquired Immunodeficiency Syndrome--metabolism mesh_headings: Acquired Immunodeficiency Syndrome--pathology mesh_headings: Cell Nucleus--genetics mesh_headings: Cell Nucleus--metabolism mesh_headings: Cohort Studies mesh_headings: Disease Progression mesh_headings: European Continental Ancestry Group--genetics mesh_headings: Female mesh_headings: Genetic Variation mesh_headings: Genotype mesh_headings: Humans mesh_headings: Male mesh_headings: Mitochondria--genetics mesh_headings: Mitochondria--metabolism mesh_headings: Polymorphism, Single Nucleotide mesh_headings: Protein Transport citation: Hendrickson, SL and Lautenberger, JA and Chinn, LW and Malasky, M and Sezgin, E and Kingsley, LA and Goedert, JJ and Kirk, GD and Gomperts, ED and Buchbinder, SP and Troyer, JL and O'Brien, SJ (2010) Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. PLoS ONE, 5 (9). 1 - 8. document_url: http://d-scholarship-dev.library.pitt.edu/13552/1/Genetic_Variants_in_Nuclear-Encoded.pdf document_url: http://d-scholarship-dev.library.pitt.edu/13552/8/licence.txt