mtDNA haplogroup J Modulates telomere length and Nitric Oxide production

Abstract

BackgroundOxidative stress due to the overproduction of nitric oxide (NO) and other oxygen reactive species (ROS), play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. Therefore, the goal of this work is to describe the difference in telomere length of peripheral blood leukocytes (PBLs) and Nitric Oxide (NO) production between mitochondrial DNA (mtDNA) haplogroup J and non-J carriers, as indirect approaches of oxidative stress.MethodsThe telomere length of PBL was analyzed in DNA samples from 166 healthy controls (114 J and 52 non-J) and 79 OA patients (41 J and 38 non-J) by means of a validated qPCR method. The NO production was assessed in 7 carriers of the haplogroup J and 27 non-J carriers, by means of the colorimetric reaction of the Griess reagent in supernatants of cultured chondrocytes. Inducible nitric oxide synthase (iNOS) mRNA from these samples was analyzed by qPCR. Appropiated statistical analyses were performedResultsCarriers of the haplogroup J showed a significantly longer telomere length of PBLs than non-J carriers, regardless of age, gender and diagnosis (p = 0.025). Cultured chondrocytes carrying the mtDNA haplogroup J also showed a lower NO production than non-J carriers (p = 0.043). No significant correlations between age and telomore length of PBLs were detected neither for carriers of the haplogroup J nor for non-J carriers. A strong positive correlation between NO production and iNOS expression was also observed (correlation coefficient = 0.791, p < 0.001).ConclusionThe protective effect of the mtDNA haplogroup J in the OA disease arise from a lower oxidative stress in carriers of this haplogroup, since this haplogroup is related to lower NO production and hence longer telomere length of PBLs too.

Mitochondrial DNA haplogroups influence the risk of incident knee osteoarthritis in OAI and CHECK cohorts. A meta-analysis and functional study

“…Subjects carrying this haplogroup have a lower prevalence of knee and/or hip OA,16 17 19 28 besides this mtDNA variant also associates with lower serum levels of catabolic type II collagen biomarkers34 and metalloproteinases (MMPs)35 and has been correlated with higher telomere length and lower nitric oxide production in articular chondrocytes 36. However, a work by Hudson et al found no evidence of associations between mtDNA variants and the risk of OA 20.…”

Comparison of telomere length between population-specific mitochondrial haplogroups among different age groups in a Latvian population

“…This hypothesis also might explain slightly longer telomeres for hg J among centenarians in the current/present study, due to less ROS accumulation during aging. Also previously, Fernández-Moreno et al have shown that individuals with hg J have significantly longer telomeres than non-J carriers (Fernández-Moreno et al, 2011). However, Pinós et al have found that hg J and longevity are not related and have proposed that different findings in previous reports could be due to a population-specific background (Pinós et al, 2012).…”

“…However, to date, only few studies have addressed the possible association of mitochondrial hgs with TL. Fernández-Moreno et al examined TL in hg J individuals and showed that they have significantly longer telomeres than non-J carriers (Fernández-Moreno et al, 2011). Considering that both cell elements are involved in the process of aging and longevity, there could be a possible association between mitochondrial inherited polymorphisms and the dynamics of TL.…”

Association between mitochondrial DNA haplogroup and myelodysplastic syndromes

“…Polymorphisms can be used to group individuals into haplogroups that reflect human global migration (van Oven and Kayser, 2009; Mitchell et al, 2014). These mitochondrial variants are associated with differences in mitochondrial function (Martinez-Redondo et al, 2010; Fernandez-Moreno et al, 2011; Gomez-Duran et al, 2012; Mueller et al, 2012; Kenney et al, 2013; Kenney et al, 2014) and have been associated with multiple diseases, including cancer (Singh and Kulawiec, 2009). One previous report in a Japanese population has suggested that mtDNA haplogroup M7b2 is associated with increased risk of hematopoietic cancer (Verma et al, 2007).…”