Basic science: HIV researchA

Basic science: HIV research

Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression

Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ. PLoS One. 2010 Sep 21;5(9):e12862.

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. Here Hendrickson and colleagues explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins influence AIDS progression among HIV-1 infected patients. They examined nuclear-encoded mitochondrial proteins 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 nuclear-encoded mitochondrial proteins genes. With a Bonferroni adjustment for the number of genes and tests examined, multiple SNPs within two nuclear-encoded mitochondrial protein 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. The authors’ previous studies on mitochondrial DNA showed that European haplogroups with presumed functional differences were associated with AIDS progression and antiretroviral therapy 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.