Mitochondrial Haplogroup Influences Motor Function in Long-Term HIV-1-Infected Individuals

Abstract

Evolutionary divergence of the mitochondrial genome has given rise to distinct haplogroups. These haplogroups have arisen in specific geographical locations and are responsible for subtle functional changes in the mitochondria that may provide an evolutionary advantage in a given environment. Based on these functional differences, haplogroups could define disease susceptibility in chronic settings. In this study, we undertook a detailed neuropsychological analysis of a cohort of long-term HIV-1-infected individuals in conjunction with sequencing of their mitochondrial genomes. Stepwise regression analysis showed that the best model for predicting both working memory and declarative memory were age and years since diagnosis. In contrast, years since diagnosis and sub-haplogroup were significantly predictive of psychomotor speed. Consistent with this, patients with haplogroup L3e obtained better scores on psychomotor speed and dexterity tasks when compared to the remainder of the cohort, suggesting that this haplogroup provides a protective advantage when faced with the combined stress of HIV-1 infection and long-term antiretroviral therapies. Differential performance on declarative memory tasks was noted for individuals with other sub-L haplogroups, but these differences were not as robust as the association between L3e and psychomotor speed and dexterity tasks. This work provides evidence that mitochondrial haplogroup is related to neuropsychological test performance among patients in chronic disease settings such as HIV-1 infection.

The association of mitochondrial DNA haplogroups with POAG in African Americans

“…The oldest haplogroups originated in Africa (L0, L1, L2, L3), with contemporary non-African haplogroups branching from L3 11 . Each haplogroup, with its own set of single nucleotide variants (SNVs), can have unique bioenergetic properties and differing interactions with nuclear influences and environmental exposures 8,14 The role of mtDNA haplogroups in POAG remains unclear, especially in African Americans. Studies in European patients 15 , Ghanaian patients 16 , and Arab patients 17 found that mtDNA haplogroups did not influence POAG susceptibility.…”