mtDNA haplogroup J modulates telomere length and nitric oxide production

BMC Musculoskelet Disord. 2011 Dec 15:12:283. doi: 10.1186/1471-2474-12-283.

Abstract

Background: Oxidative 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.

Methods: The 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 performed

Results: Carriers 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).

Conclusion: The 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Colorimetry
  • DNA, Mitochondrial / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes*
  • Humans
  • Leukocytes / metabolism*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Osteoarthritis, Hip / diagnosis
  • Osteoarthritis, Hip / genetics*
  • Osteoarthritis, Hip / metabolism*
  • Oxidative Stress*
  • Phenotype
  • Polymerase Chain Reaction
  • Regression Analysis
  • Spain
  • Telomere / metabolism*
  • Telomere Shortening
  • Young Adult

Substances

  • DNA, Mitochondrial
  • Nitric Oxide
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II