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.
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.
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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Hendrickson, SL | | | | | Lautenberger, JA | | | | | Chinn, LW | | | | | Malasky, M | | | | | Sezgin, E | | | | | Kingsley, LA | kingsley@pitt.edu | KINGSLEY | | | Goedert, JJ | | | | | Kirk, GD | | | | | Gomperts, ED | | | | | Buchbinder, SP | | | | | Troyer, JL | | | | | O'Brien, SJ | | | |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID |
|---|
| Editor | Badger, Jonathan H. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
| Date: |
29 October 2010 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS ONE |
| Volume: |
5 |
| Number: |
9 |
| Page Range: |
1 - 8 |
| DOI or Unique Handle: |
10.1371/journal.pone.0012862 |
| Schools and Programs: |
School of Public Health > Epidemiology
School of Public Health > Infectious Diseases and Microbiology |
| Refereed: |
Yes |
| MeSH Headings: |
Acquired Immunodeficiency Syndrome--genetics; Acquired Immunodeficiency Syndrome--metabolism; Acquired Immunodeficiency Syndrome--pathology; Cell Nucleus--genetics; Cell Nucleus--metabolism; Cohort Studies; Disease Progression; European Continental Ancestry Group--genetics; Female; Genetic Variation; Genotype; Humans; Male; Mitochondria--genetics; Mitochondria--metabolism; Polymorphism, Single Nucleotide; Protein Transport |
| Other ID: |
NLM PMC2943476 |
| PubMed Central ID: |
PMC2943476 |
| PubMed ID: |
20877624 |
| Date Deposited: |
21 Aug 2012 14:16 |
| Last Modified: |
02 Feb 2019 15:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/13552 |
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