TY - JOUR
T1 - Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression
AU - Hendrickson, Sher L.
AU - Lautenberger, James A.
AU - Chinn, Leslie Wei
AU - Malasky, Michael
AU - Sezgin, Efe
AU - Kingsley, Lawrence A.
AU - Goedert, James J.
AU - Kirk, Gregory D.
AU - Gomperts, Edward D.
AU - Buchbinder, Susan P.
AU - Troyer, Jennifer L.
AU - O'Brien, Stephen J.
N1 - Funding Information:
The study group consisted of total of 1455 patients of European ancestry from five longitudinal cohorts including the Multicenter AIDS Cohort Study (MACS) , the San Francisco City Clinic Study (SFCC) , Hemophilia Growth and Development Study (HGDS) , the Multicenter Hemophilia Cohort Study (MHCS), and the AIDS Linked to Intravenous Experiences (ALIVE) cohort () . Informed written consent was obtained from all patients. HIV/AIDS-related genetic studies of the cohorts has been granted by the NIH Office of Human Subjects Research under # 4010 (OHSR #4010). Ninety-seven percent of patients were male. There are two cohorts of subjects with hemophilia who contracted AIDS principally through exposure to contaminated blood products between 1978 and 1983: the MHCS is a multi-center longitudinal cohort study enrolling subjects from 17 American or European treatment centers beginning in September 1982 and HGDS is a US-based multicenter cohort of participants from 14 US treatment centers who became infected between 1982–1983. Sexual transmission in men who have sex with men is the primary mode of HIV infection for MACS and SFCC, while intravenous drug use is the principal mode of transmission in ALIVE.
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/77958461512
UR - https://www.scopus.com/pages/publications/77958461512#tab=citedBy
U2 - 10.1371/journal.pone.0012862
DO - 10.1371/journal.pone.0012862
M3 - Article
C2 - 20877624
AN - SCOPUS:77958461512
SN - 1932-6203
VL - 5
SP - 1
EP - 8
JO - PloS one
JF - PloS one
IS - 9
M1 - e12862
ER -