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- Title
The Role of Mitochondrial DNA Variation in Age-Related Decline in Gait Speed Among Older Men Living With Human Immunodeficiency Virus.
- Authors
Sun, Jing; Brown, Todd T; Samuels, David C; Hulgan, Todd; D'Souza, Gypsyamber; Jamieson, Beth D; Erlandson, Kristine M; Martinson, Jeremy; Palella, Frank J; Margolick, Joseph B
- 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.
- Subjects
AIDS diagnosis; HEPATITIS C prevention; AGE distribution; BODY composition; CONFIDENCE intervals; DNA; GENETIC polymorphisms; GENOMES; HIV-positive persons; LONGITUDINAL method; MITOCHONDRIA; NEURITIS; PROBABILITY theory; SMOKING; WHITE people; LOGISTIC regression analysis; MULTIPLE regression analysis; EDUCATIONAL attainment; HIV seroconversion; HAPLOTYPES; DEOXYRIBONUCLEOSIDES; ODDS ratio; GENOTYPES
- Publication
Clinical Infectious Diseases, 2018, Vol 67, Issue 5, p778
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciy151