Analysis of the mitochondrial DNA genome in the peripheral blood leukocytes of HIV-infected patients with or without lipoatrophy,

Abstract Mitochondria play multiple important cellular functions. The purpose of this study was to evaluate whether leukocyte mitochondrial DNA copy number (mtDNAcn) is associated with aggressive prostate cancer (PCa) in African American (AA) men. We measured the mtDNAcn in peripheral blood leukocytes from 317 localized AA PCa patients and evaluated its associations with aggressive disease features at diagnosis and biochemical recurrence (BCR) after treatments. There was no significant difference in mtDNAcn among the clinical features at diagnosis, including age, prostate-specific antigen level, Gleason score and clinical stage under analysis of variance test. However, mtDNAcn was significantly associated with BCR in multivariate Cox analysis. Dichotomized into low and high mtDNAcn groups by the median value of mtDNAcn, patients with low mtDNAcn exhibited a significantly lower risk of BCR (hazard ratio = 0.32, 95% confidence interval: 0.13–0.79) compared to those with high mtDNAcn. There was a significant dose–response in tertile and quartile analyses (P for trend = 0.012 and 0.002, respectively). In Kaplan–Meier survival analyses, patients with higher mtDNAcn exhibited significantly shorter BCR-free survival time than those with lower mtDNAcn in dichotomous, tertile and quartile analyses, with long-rank P values of 0.017, 0.024 and 0.019, respectively. Our results showed for the first time that high leukocyte mtDNAcn was associated with worse prognosis in AA PCa patients.

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Relationship between the dynamics of telomere loss in peripheral blood leukocytes from osteoarthritis patients and mitochondrial DNA haplogroup

The Journal of Rheumatology ◽

10.3899/jrheum.201316 ◽

2021 ◽

pp. jrheum.201316

Author(s):

Rebeca Guillén Fajardo ◽

Fátima Otero Fariña ◽

Alejandro Mosquera Rey ◽

Ignacio Rego-Pérez ◽

Francisco Javier Blanco García ◽

...

Keyword(s):

Mitochondrial Dna ◽

Multivariate Analysis ◽

Peripheral Blood ◽

Binary Logistic Regression ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Knee Oa ◽

Telomere Sequence ◽

Telomere Loss

Objective The evaluation of the evolution of telomere length from peripheral blood leukocytes (PBL) in subjects from the Osteoarthritis Initiative (OAI) cohort in relation to the incidence of osteoarthritis (OA) and explore its possible interactive influence with the mitochondrial DNA (mtDNA) haplogroup. Methods Dynamics of telomere sequence loss was quantified in PBL from initially healthy individuals, without symptoms or radiological signs, 78 carrying the mtDNA cluster HV and 47 with cluster JT, from the OAI, during a 72-month follow-up. The incidence of knee OA during this period (n=39) was radiographically established when Kellgren-Lawrence (KL) score increased from < 2 at recruitment to ≥ 2 during 72 months of follow-up. Multivariate analysis using binary logistic regression was performed to assess PBL telomere loss and mtDNA haplogroups as associated risk factors of incidence of knee OA Results Carriers of cluster HV showed an OA incidence twice that of the JT carriers (n=30 vs. n=9). Rate of PBL telomere loss was higher in cluster HV carriers and in incident individuals. Multivariate analysis showed that the dynamics of PBL telomere shortening can be a consistent risk marker of knee OA incidence. Non-incidents showed a slower telomere loss than incidents, the difference being more significant in carriers of cluster JT than in HV. Conclusion An increased telomere loss rate in PBL may reflect a systemic accelerated senescence phenotype which could be potentiated by the mitochondrial function, increasing the susceptibility of developing OA.

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