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The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus.
Clin Infect Dis. 2018 08 16; 67(5):778-784.CI

Abstract

Background

Age-related gait speed decline is accelerated in men with human immunodeficiency virus (HIV). Mitochondrial genetic variation is associated with frailty and mortality in the general population and may provide insight into mechanisms of functional decline in people aging with HIV.

Methods

Gait speed was assessed semiannually in the Multicenter AIDS Cohort Study. Mitochondrial DNA (mtDNA) haplogroups were extracted from genome-wide genotyping data, classifying men aged ≥50 years into 5 groups: mtDNA haplogroup H, J, T, Uk, and other. Differences in gait speed by haplogroups were assessed as rate of gait speed decline per year, probability of slow gait speed (<1.0 m/s), and hazard of slow gait using multivariable linear mixed-effects models, mixed-effects logistic regression models, and the Andersen-Gill model, controlling for hepatitis C virus infection, previous AIDS diagnosis, thymidine analogues exposure, education, body composition, smoking, and peripheral neuropathy. Age was further controlled for in the mixed-effects logistic regression models.

Results

A total of 455 HIV-positive white men aged ≥50 years contributed 3283 person-years of follow-up. Among them, 70% had achieved HIV viral suppression. In fully adjusted models, individuals with haplogroup J had more rapid decline in gait speed (adjusted slopes, 0.018 m/s/year vs 0.011 m/s/year, pinteraction = 0.012) and increased risk of developing slow gait (adjusted odds ratio, 2.97; 95% confidence interval, 1.24-7.08) compared to those with other haplogroups.

Conclusions

Among older, HIV-infected men, mtDNA haplogroup J was an independent risk factor for more rapid age-related gait speed decline.

Authors+Show Affiliations

Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. Johns Hopkins University School of Medicine, Baltimore, Maryland.Vanderbilt Genetics Institute, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.Vanderbilt University Medical Center, Nashville, Tennessee.Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.David Geffen School of Medicine, University of California-Los Angeles.University of Colorado Anschutz Medical Campus, Aurora.University of Pittsburgh, Graduate School of Public Health, Pennsylvania.Northwestern University Feinberg School of Medicine, Chicago, Illinois.Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. Johns Hopkins University School of Medicine, Baltimore, Maryland.Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland.

Pub Type(s)

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

Language

eng

PubMed ID

29481608

Citation

Sun, Jing, et al. "The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 67, no. 5, 2018, pp. 778-784.
Sun J, Brown TT, Samuels DC, et al. The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus. Clin Infect Dis. 2018;67(5):778-784.
Sun, J., Brown, T. T., Samuels, D. C., Hulgan, T., D'Souza, G., Jamieson, B. D., Erlandson, K. M., Martinson, J., Palella, F. J., Margolick, J. B., Kirk, G. D., & Schrack, J. A. (2018). The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 67(5), 778-784. https://doi.org/10.1093/cid/ciy151
Sun J, et al. The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus. Clin Infect Dis. 2018 08 16;67(5):778-784. PubMed PMID: 29481608.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus. AU - Sun,Jing, AU - Brown,Todd T, AU - Samuels,David C, AU - Hulgan,Todd, AU - D'Souza,Gypsyamber, AU - Jamieson,Beth D, AU - Erlandson,Kristine M, AU - Martinson,Jeremy, AU - Palella,Frank J,Jr AU - Margolick,Joseph B, AU - Kirk,Gregory D, AU - Schrack,Jennifer A, PY - 2017/11/04/received PY - 2018/02/21/accepted PY - 2018/2/27/pubmed PY - 2019/10/28/medline PY - 2018/2/27/entrez SP - 778 EP - 784 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin Infect Dis VL - 67 IS - 5 N2 - Background: Age-related gait speed decline is accelerated in men with human immunodeficiency virus (HIV). Mitochondrial genetic variation is associated with frailty and mortality in the general population and may provide insight into mechanisms of functional decline in people aging with HIV. Methods: Gait speed was assessed semiannually in the Multicenter AIDS Cohort Study. Mitochondrial DNA (mtDNA) haplogroups were extracted from genome-wide genotyping data, classifying men aged ≥50 years into 5 groups: mtDNA haplogroup H, J, T, Uk, and other. Differences in gait speed by haplogroups were assessed as rate of gait speed decline per year, probability of slow gait speed (<1.0 m/s), and hazard of slow gait using multivariable linear mixed-effects models, mixed-effects logistic regression models, and the Andersen-Gill model, controlling for hepatitis C virus infection, previous AIDS diagnosis, thymidine analogues exposure, education, body composition, smoking, and peripheral neuropathy. Age was further controlled for in the mixed-effects logistic regression models. Results: A total of 455 HIV-positive white men aged ≥50 years contributed 3283 person-years of follow-up. Among them, 70% had achieved HIV viral suppression. In fully adjusted models, individuals with haplogroup J had more rapid decline in gait speed (adjusted slopes, 0.018 m/s/year vs 0.011 m/s/year, pinteraction = 0.012) and increased risk of developing slow gait (adjusted odds ratio, 2.97; 95% confidence interval, 1.24-7.08) compared to those with other haplogroups. Conclusions: Among older, HIV-infected men, mtDNA haplogroup J was an independent risk factor for more rapid age-related gait speed decline. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/29481608/The_Role_of_Mitochondrial_DNA_Variation_in_Age_Related_Decline_in_Gait_Speed_Among_Older_Men_Living_With_Human_Immunodeficiency_Virus_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciy151 DB - PRIME DP - Unbound Medicine ER -