Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression

• Published in: PloS one 2010-09, Vol.5 (9), p.e12862
• Main Authors: Hendrickson, Sher L, Lautenberger, James A, Chinn, Leslie Wei, Malasky, Michael, Sezgin, Efe, Kingsley, Lawrence A, Goedert, James J, Kirk, Gregory D, Gomperts, Edward D, Buchbinder, Susan P, Troyer, Jennifer L, O'Brien, Stephen J
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - genetics; Acquired Immunodeficiency Syndrome - metabolism; Acquired Immunodeficiency Syndrome - pathology; AIDS; AIDS (Disease); Antigens; Apoptosis; Biosynthesis; Breast cancer; Cell Nucleus - genetics; Cell Nucleus - metabolism; Chromosome 12; Chromosome 6; Cloning; Cohort Studies; Deoxyribonucleic acid; Development and progression; Disease Progression; DNA; Epidemiology; Fatty acids; Female; Gene expression; Genes; Genetic aspects; Genetic diversity; Genetic variance; Genetic Variation; Genetics and Genomics/Genetics of Disease; Genetics and Genomics/Genome Projects; Genomes; Genomics; Genotype; Genotypes; Genotyping; Haplotypes; Hemophilia; Highly active antiretroviral therapy; HIV; HIV patients; Human immunodeficiency virus; Humans; Infections; Infectious Diseases/HIV Infection and AIDS; Laboratories; Liver cancer; Male; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial DNA; Multiculturalism & pluralism; Pathogenesis; Patients; Polymorphism, Single Nucleotide; Principal components analysis; Protein Transport; Proteins; Public health; Quantitative analysis; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; White People - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012862

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 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. 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.