Mitochondrial DNA haplogroups and domain-specific neurocognitive performance in adults with HIV - PubMed (original) (raw)

Observational Study

Mitochondrial DNA haplogroups and domain-specific neurocognitive performance in adults with HIV

Karen Volpe et al. J Neurovirol. 2021 Aug.

Abstract

Neurocognitive (NC) impairment (NCI) is an important cause of morbidity in persons with HIV (PWH). In the high-energy environment of the central nervous system, mitochondria contribute to neuroinflammation and aging, which may ultimately drive the pathogenesis of neurodegenerative diseases. Mitochondrial DNA (mtDNA) haplogroups are associated with health outcomes in PWH. For example, we previously observed less global NCI in Hispanic ancestry PWH having mtDNA haplogroup B. Another study reported increased NCI among PWH having African subhaplogroup L2a. We therefore analyzed NC domains in relation to these haplogroups in CNS HIV Antiretroviral Therapy Effects Research (CHARTER), a multi-site observational neuro-HIV study. Haplogroups were assigned using mtDNA sequence in 1016 PWH. Outcomes were NCI, defined by domain deficit score and mean T-scores (TS) for seven NC domains. Ancestry-stratified analyses of NC performance included Wilcoxon rank sum, χ2, and Fisher's exact tests. Multivariable regression adjusted for NC comorbidity, antiretroviral therapy use, and nadir CD4+ T cells. Among 98 Hispanic ancestry PWH, executive function, learning, and recall performance were better with haplogroup B (N = 17) than other haplogroups. With adjustment for covariates, haplogroup B remained associated with better executive function (p = 0.04) and recall TS (p = 0.03). PWH with haplogroup B had fewer impaired domains than other haplogroups (p < 0.01). Subhaplogroup L2a (N = 89) was associated with greater NCI in learning, recall, and working memory among 478 PWH of African ancestry, and had more impaired domains than other subhaplogroups (p < 0.01). These findings may inform risk stratification for NCI and studies to define mechanisms by which mtDNA variation may influence NCI in PWH.

Keywords: African Americans; DNA; HIV; Hispanic Americans; Mitochondrial; Neurocognitive disorders.

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Conflict of interest statement

The authors report no potential conflicts of interest relevant to the work.

Figures

Figure 1.

Executive function, learning, and delayed recall domain performance by T-scores (Panel A) and proportion with domain-specific impairment (Panel B), by mtDNA haplogroup B within persons of Hispanic ancestry.

Figure 2.

Learning, recall memory, and working memory domain performance by T-scores (Panel A) and proportion with domain-specific impairment (Panel B), by mtDNA haplogroup L2a within persons of African ancestry.

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Mitochondrial DNA haplogroups and domain-specific neurocognitive performance in adults with HIV - PubMed (original) (raw)