title: Mitochondrial Haplogroup Influences Motor Function in Long-Term HIV-1-Infected Individuals.
abstract: Evolutionary divergence of the mitochondrial genome has given rise to distinct haplogroups. These haplogroups have arisen in specific geographical locations and are responsible for subtle functional changes in the mitochondria that may provide an evolutionary advantage in a given environment. Based on these functional differences, haplogroups could define disease susceptibility in chronic settings. In this study, we undertook a detailed neuropsychological analysis of a cohort of long-term HIV-1-infected individuals in conjunction with sequencing of their mitochondrial genomes. Stepwise regression analysis showed that the best model for predicting both working memory and declarative memory were age and years since diagnosis. In contrast, years since diagnosis and sub-haplogroup were significantly predictive of psychomotor speed. Consistent with this, patients with haplogroup L3e obtained better scores on psychomotor speed and dexterity tasks when compared to the remainder of the cohort, suggesting that this haplogroup provides a protective advantage when faced with the combined stress of HIV-1 infection and long-term antiretroviral therapies. Differential performance on declarative memory tasks was noted for individuals with other sub-L haplogroups, but these differences were not as robust as the association between L3e and psychomotor speed and dexterity tasks. This work provides evidence that mitochondrial haplogroup is related to neuropsychological test performance among patients in chronic disease settings such as HIV-1 infection.
authors.affiliation: Department of Pathology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ashley
authors.initials: A
authors.lastname: Azar
authors.affiliation: Department of Psychology, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Kathryn
authors.identifier: http://orcid.org/0000-0003-1722-6316
authors.initials: K
authors.lastname: Devlin
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Center for Genomic Sciences, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Joshua Chang
authors.identifier: http://orcid.org/0000-0003-0222-5636
authors.initials: JC
authors.lastname: Mell
authors.affiliation: Department of Psychology, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Tania
authors.initials: T
authors.lastname: Giovannetti
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pirrone
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Nonnemacher
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Shendra
authors.initials: S
authors.lastname: Passic
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kercher
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jean W
authors.initials: JW
authors.lastname: Williams
authors.affiliation: Department of Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America.|Department of Neuroscience, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jeffery M
authors.identifier: http://orcid.org/0000-0001-5293-4866
authors.initials: JM
authors.lastname: Jacobson
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Wigdahl
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Dampier
authors.affiliation: Department of Geriatrics and Gerontology, New Jersey Institute for Successful Aging, School of Osteopathic Medicine, Rowan University, Stratford, New Jersey, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Libon
authors.affiliation: Department of Pathology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Christian
authors.initials: C
authors.lastname: Sell
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D015497:HIV-1 / Q000502:physiology*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D009043:Motor Activity / Q000235:genetics*