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Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection.
Clin Infect Dis. 2015 Nov 01; 61(9):1476-84.CI

Abstract

BACKGROUND

Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort.

METHODS

CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir.

RESULTS

Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm(3), 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P < .001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = -0.34; P = .008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval, .04, .63; P = .009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry.

CONCLUSIONS

In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons.

Authors+Show Affiliations

Vanderbilt University, Nashville, Tennessee.Vanderbilt University, Nashville, Tennessee.Vanderbilt University, Nashville, Tennessee.University of California-San Diego, California.University of California-San Diego, California.University of California-San Diego, California.University of California-San Diego, California.Vanderbilt University, Nashville, Tennessee.Vanderbilt University, Nashville, Tennessee.Washington University, St. Louis, Missouri.University of Washington, Seattle.University of Texas Medical Branch, Galveston.University of Washington, Seattle.Johns Hopkins University, Baltimore, Maryland.University of California-San Diego, California.Icahn School of Medicine at Mount Sinai, New York, New York.Icahn School of Medicine at Mount Sinai, New York, New York.University of California-San Diego, California.Cleveland Clinic Foundation/Lerner Research Institute and Cleveland Clinic Lerner College of Medicine, Ohio.No affiliation info available

Pub Type(s)

Journal Article
Observational Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26129753

Citation

Hulgan, Todd, et al. "Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 61, no. 9, 2015, pp. 1476-84.
Hulgan T, Samuels DC, Bush W, et al. Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection. Clin Infect Dis. 2015;61(9):1476-84.
Hulgan, T., Samuels, D. C., Bush, W., Ellis, R. J., Letendre, S. L., Heaton, R. K., Franklin, D. R., Straub, P., Murdock, D. G., Clifford, D. B., Collier, A. C., Gelman, B. B., Marra, C. M., McArthur, J. C., McCutchan, J. A., Morgello, S., Simpson, D. M., Grant, I., & Kallianpur, A. R. (2015). Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 61(9), 1476-84. https://doi.org/10.1093/cid/civ527
Hulgan T, et al. Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection. Clin Infect Dis. 2015 Nov 1;61(9):1476-84. PubMed PMID: 26129753.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection. AU - Hulgan,Todd, AU - Samuels,David C, AU - Bush,William, AU - Ellis,Ronald J, AU - Letendre,Scott L, AU - Heaton,Robert K, AU - Franklin,Donald R, AU - Straub,Peter, AU - Murdock,Deborah G, AU - Clifford,David B, AU - Collier,Ann C, AU - Gelman,Benjamin B, AU - Marra,Christina M, AU - McArthur,Justin C, AU - McCutchan,J Allen, AU - Morgello,Susan, AU - Simpson,David M, AU - Grant,Igor, AU - Kallianpur,Asha R, AU - ,, Y1 - 2015/06/30/ PY - 2015/04/01/received PY - 2015/06/22/accepted PY - 2015/7/2/entrez PY - 2015/7/2/pubmed PY - 2016/7/28/medline KW - AIDS KW - DNA, mitochondrial KW - HIV KW - cognitive disorders SP - 1476 EP - 84 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin Infect Dis VL - 61 IS - 9 N2 - BACKGROUND: Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. METHODS: CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir. RESULTS: Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm(3), 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P < .001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = -0.34; P = .008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval, .04, .63; P = .009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry. CONCLUSIONS: In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/26129753/Mitochondrial_DNA_Haplogroups_and_Neurocognitive_Impairment_During_HIV_Infection_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/civ527 DB - PRIME DP - Unbound Medicine ER -