Correlates of Peripheral Blood Mitochondrial DNA Content in a General Population

Abstract

Accumulation of mitochondrial DNA (mtDNA) mutations leads to alterations of mitochondrial biogenesis and function that might produce a decrease in mtDNA content within cells. This implies that mtDNA content might be a potential biomarker associated with oxidative stress and inflammation. However, data on correlates of mtDNA content in a general population are sparse. Our goal in the present study was to describe in a randomly recruited population sample the distribution and determinants of peripheral blood mtDNA content. From 2009 to 2013, we examined 689 persons (50.4% women; mean age = 54.4 years) randomly selected from a Flemish population (Flemish Study on Environment, Genes, and Health Outcomes). Relative mtDNA copy number as compared with nuclear DNA was measured by quantitative real-time polymerase chain reaction in peripheral blood. There was a curvilinear relationship between relative mtDNA copy number and age. mtDNA content slightly increased until the fifth decade of life and declined in older subjects (Page (2) = 0.0002). mtDNA content was significantly higher in women (P = 0.007) and increased with platelet count (P < 0.0001), whereas it was inversely associated with white blood cell count (P < 0.0001). We also observed lower mtDNA content in women using estroprogestogens (P = 0.044). This study demonstrated in a general population that peripheral blood mtDNA content is significantly associated with sex and age. Blood mtDNA content is also influenced by platelet and white blood cell counts and estroprogestogen intake. Further studies are required to clarify the impact of chronic inflammation and hormone therapy on mitochondrial function.

Keywords: general population; mitochondrial DNA; peripheral blood.

Figure 1.

Distribution of the relative mitochondrial DNA (mtDNA) content (ratio of copy numbers) among women (A) and men (B) in the Flemish Study on Environment, Genes, and Health Outcomes, 2009–2013. The curves represent the fitted normal (full line) and Kernel (dashed line) density plots. In women, the coefficients of skewness and kurtosis were 1.37 (P < 0.01) and 2.94, respectively. In men, the coefficients of skewness and kurtosis were 1.18 (P < 0.01) and 2.61, respectively.

Figure 2.

Mean mitochondrial DNA (mtDNA) content (ratio of copy numbers; see Methods), by age, in the Flemish Study on Environment, Genes, and Health Outcomes, 2009–2013. Results were adjusted for sex, white blood cell and platelet counts, use of systemic hormone therapy, and family clusters. The numbers of individuals in the age groups were: ≤40 years, n = 133; 40.1–50.0 years, n = 113; 50.1–60.0 years, n = 180; 60.1–70.0 years, n = 150; and ≥70.1 years, n =113. Bars, standard errors.

Figure 3.

Relative mitochondrial DNA (mtDNA) content (ratio of copy numbers; see Methods) according to white blood cell (WBC) count (A) (r = −0.24, P = <0.0001) and platelet count (B) (r = 0.15, P = <0.0001) in multivariable-adjusted analyses in the Flemish Study on Environment, Genes, and Health Outcomes, 2009–2013. The solid and dashed lines represent the regression line and the 95% confidence interval, respectively. Analyses were adjusted for age, age², sex, use of systemic hormone therapy, and family clusters. In addition, for WBC count, the adjusted model included platelet count. For platelet count, the adjusted model included WBC count.

Figure 4.

Multivariable-adjusted relative mitochondrial DNA (mtDNA) content (ratio of copy numbers; see Methods), by sex (A) and use of systemic hormone therapy (SHT) (B), among women in the Flemish Study on Environment, Genes, and Health Outcomes, 2009–2013. Results were adjusted for sex, age, age², white blood cell and platelet counts, and family clusters. In part A, the P value for the difference between men (n = 342) and women (n = 347) was 0.013. In part B, the P value for the difference between women using SHT (n = 290) and women not using SHT (n = 57) was 0.044.