Mitochondrial DNA Haplogroup M7 Confers Disability in a Chinese Aging Population

Abstract

Mitochondrial DNA (mtDNA) haplogroups have been associated with functional impairments (i.e., decreased gait speed and grip strength, frailty), which are risk factors of disability. However, the association between mtDNA haplogroups and ADL disability is still unclear. In this study, we conducted an investigation of 25 mtSNPs defining 17 major mtDNA haplogroups for ADL disability in an aging Chinese population. We found that mtDNA haplogroup M7 was associated with an increased risk of disability (OR = 3.18 [95% CI = 1.29-7.83], P = 0.012). The survival rate of the M7 haplogroup group (6.1%) was lower than that of the non-M7 haplogroup group (9.5%) after a 6-year follow-up. In cellular studies, cytoplasmic hybrid (cybrid) cells with the M7 haplogroup showed distinct mitochondrial functions from the M8 haplogroup. Specifically, the respiratory chain complex capacity was significantly lower in M7 haplogroup cybrids than in M8 haplogroup cybrids. Furthermore, an obvious decreased mitochondrial membrane potential and 40% reduced ATP-linked oxygen consumption were found in M7 haplogroup cybrids compared to M8 haplogroup cybrids. Notably, M7 haplogroup cybrids generated more reactive oxygen species (ROS) than M8 haplogroup cybrids. Therefore, the M7 haplogroup may contribute to the risk of disability via altering mitochondrial function to some extent, leading to decreased oxygen consumption, but increased ROS production, which may activate mitochondrial retrograde signaling pathways to impair cellular and tissue function.

Mitochondrial DNA haplogroup M7 confers a reduced risk of colorectal cancer in a Han population from northern China

“…We have previously found that haplogroup M7 was associated with a significant reduction in the risk of liver cancer in Northern China 31 . More recently, Sun et al reported that haplogroup M7 is associated with an increased risk of disability in an ageing Chinese population 32 . In this study, we further found that haplogroup M7 was associated with a reduced risk of CRC.…”

“…31 More recently, Sun et al reported that haplogroup M7 is associated with an increased risk of disability in an ageing Chinese population. 32 In this study, we further found that haplogroup M7 was associated with a reduced risk of CRC. Thus, our results provide further evidence for the involvement of mtDNA haplogroup M7 in ageingrelated human diseases, especially cancer.…”

“…Interestingly, it has been reported that, compared to haplogroup M8, haplogroup M7 has a significantly lower respiratory chain activity and lower mitochondrial membrane potential, together with a 40% reduction in respiration‐related oxygen consumption. These findings hint that mitochondrial haplogroup M7 may reduce the risk of CRC due to the presence of sub‐optimal mitochondrial functionality in this haplogroup 32 . Lower mitochondrial function may promote tumorigenesis due to altered mitochondrial signals including ROS and NAD + /NADH, which are responsible for overactivation of mitochondrial retrograde signaling 36 .…”

“…These findings hint that mitochondrial haplogroup M7 may reduce the risk of CRC due to the presence of sub-optimal mitochondrial functionality in this haplogroup. 32…”

The Mitochondrial tRNAPhe 625G>A Mutation in Three Han Chinese Families With Cholecystolithiasis

“…Mitochondrial haplogroup J was associated with a higher risk of obesity in the Qatari population( Dashti et al, 2021 ). Mitochondrial DNA Haplogroup M7 Confers Disability in a Chinese Aging Population( Sun et al, 2020 ). Here, these mitochondrial genomes of A6, A7, and A40 pedigrees belong to the Eastern Asian haplogroups H2, F4b, and M10a, respectively.…”