Tight co-twin similarity of monozygotic twins for hTERT protein level of T cell subsets, for telomere length and mitochondrial DNA copy number, but not for telomerase activity

Cell Mol Life Sci. 2018 Jul;75(13):2447-2456. doi: 10.1007/s00018-017-2738-z. Epub 2017 Dec 30.

Abstract

Our study analyzed lymphocyte subpopulations of 32 monozygotic twins and compared the level of the catalytic reverse transcriptase protein subunit (hTERT) in T lymphocytes (Tly), helper- (Th), cytotoxic- (Tc) and regulatory T cell (Treg) subgroups. Four variables related to telomere and mitochondrial biology were simultaneously assessed, applying multi-parametric flow cytometry, TRAP-ELISA assay and qPCR standard curve method on peripheral blood mononuclear cell (PBMC) samples of genetically matched individuals. Twin data of telomerase activity (TA), hTERT protein level, telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were analyzed for co-twin similarity. The present study has provided novel information by demonstrating very high intraclass correlation (ICC) of hTERT protein level in T lymphocytes (0.891) and in both Th (0.896), Treg (0.885) and Tc (0.798) cell subgroups. When comparing results measured from PBMCs, intraclass correlation was also high for telomere length (0.815) and considerable for mtDNA copy number (0.524), and again exceptionally high for the rate-limiting telomerase subunit, hTERT protein level (0.946). In contrast, telomerase activity showed no co-twin similarity (ICC 0). By comparing relative amounts of hTERT protein levels in different lymphocyte subgroups of twin subjects, in Treg cells significantly higher level could be detected compared to Tly, Th or Tc cell subgroups. This is the first study that simultaneously analyzed co-twin similarity in MZ twins for the above four variables and alongside assessed their relationship, whereby positive association was found between TL and mtDNAcn.

Keywords: Epigenetics; Mitochondrial DNA copy number; Regulatory T cells; T Lymphocytes; Telomerase activity; Telomere length; Telomere-independent functions of telomerase; Twin studies; hTERT.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cells, Cultured
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Female
  • Gene Dosage
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / metabolism*
  • Telomerase / genetics*
  • Telomerase / metabolism
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomere Homeostasis
  • Twins, Monozygotic*
  • Young Adult

Substances

  • DNA, Mitochondrial
  • TERT protein, human
  • Telomerase