The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus.

Sun J, Brown TT, Samuels DC, Hulgan T, D'Souza G, Jamieson BD, Erlandson KM, Martinson J, Palella FJ, Margolick JB, Kirk GD, Schrack JA
Clin Infect Dis. 2018 67 (5): 778-784

PMID: 29481608 · PMCID: PMC6093993 · DOI:10.1093/cid/ciy151

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.

MeSH Terms (16)

Age Factors Aging Body Composition Cohort Studies DNA, Mitochondrial Genetic Variation Haplotypes HIV Infections Humans Logistic Models Male Middle Aged Odds Ratio Risk Factors Sexual and Gender Minorities Walking Speed

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