April 2014
Volume 55, Issue 13
Jump To...
Free
ARVO Annual Meeting Abstract  |   April 2014
Different Epigenetic Methylation Patterns in Cells with African versus European Inherited Mitochondrial DNA Haplogroups: Possible Mechanism for Disease Susceptibilities?
Cristina M Kenney; Deepika Malik; Shari Atilano; Javier Caceres del Carpio; Marilyn Chwa; Anthony B Nesburn; David S Boyer; Baruch Kuppermann; Nitin Udar
Author Affiliations & Notes
  • Cristina M Kenney
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA
    Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA
  • Deepika Malik
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA
  • Shari Atilano
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA
  • Javier Caceres del Carpio
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA
  • Marilyn Chwa
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA
  • Anthony B Nesburn
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA
    Cedars-Sinai Medical Center, Los Angeles, CA
  • David S Boyer
    Retina-Vitreous Associates Medical Group, Beverly Hills, CA
  • Baruch Kuppermann
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA
  • Nitin Udar
    Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA
  • Footnotes
    Commercial Relationships Cristina Kenney, None; Deepika Malik, None; Shari Atilano, None; Javier Caceres del Carpio, None; Marilyn Chwa, None; Anthony Nesburn, None; David Boyer, None; Baruch Kuppermann, Alcon (C), Alimera (C), Allegro (C), Allergan (C), Genentech (C), Glaukos (C), GSK (F), Neurotech (C), Novagali (C), Novartis (C), Ophthotech (C), Pfizer (C), Regeneron (C), Santen (C), SecondSight (C), Teva (C), ThromboGenics (C); Nitin Udar, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2189. doi:
  • Views
  • Share
  • Tools
    • Alerts
      User Alerts
      You are adding an alert for:
      Different Epigenetic Methylation Patterns in Cells with African versus European Inherited Mitochondrial DNA Haplogroups: Possible Mechanism for Disease Susceptibilities?
      You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account
      The alert will be sent to:
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation
      Citation

      Cristina M Kenney, Deepika Malik, Shari Atilano, Javier Caceres del Carpio, Marilyn Chwa, Anthony B Nesburn, David S Boyer, Baruch Kuppermann, Nitin Udar; Different Epigenetic Methylation Patterns in Cells with African versus European Inherited Mitochondrial DNA Haplogroups: Possible Mechanism for Disease Susceptibilities?. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2189.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

      ×
    • Get Permissions
  • Supplements
Abstract
 
Purpose
 

Recent studies comparing cybrids (cytoplasmic hybrids) with H haplogroup (most common European) versus L haplogroup (African origin) showed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human ocular diseases (Kenney et al. BBA, 2013). These findings support our hypothesis that mitochondrial (mt) DNA haplogroups, representing populations from different geographic origins, may play a role in differential susceptibilities to eye diseases. Epigenetic regulation is a global cellular mechanism by which gene expression is altered without changes in nucleotide sequence. The present study was conducted to determine if cybrids with mtDNA haplogroups H versus L show differences in expression levels of methylation genes, which are important for epigenetic modification of nuclear genes.

 
Methods
 

Cybrids were created by fusing Rho0 ARPE-19 cells (depleted of mitochondria) with platelets isolated from haplogroup H (n=3) or L (n=3) individuals. The haplogroup profiles were determined with PCR and restriction enzyme digestion. Global DNA methylation status was detected using the MethylFlash Methylated DNA Quantification Kit. Q-PCR for six methylation genes was performed.

 
Results
 

L cybrids showed significantly higher global methylation (5-methyC%) compared to H cybrids (difference between mean = -0.0154 ± 0.0025, p=0.001). L cybrids had lower expression levels for HDAC1 (0.43-fold, p=0.008), HDAC6 (0.55-fold, p=0.0140, HDAC11 (0.4-fold, p=0.004), SIN3A (0.43-fold, p=0.006), MBD4 (0.68-fold, p=0.007) and higher levels for MAT2B (1.44-fold, p=0.006) compared to the H cybrids.

 
Conclusions
 

Transmitochondrial cybrids, which have identical nuclei but either H (European origin) or L (African origin) mtDNA haplogroups, have different total global methylation levels and different expression levels of key methylation genes. These findings support the hypothesis that mtDNA variants can induce epigenetic changes in the nucleus and act as a “modifier” for nuclear gene expression to contribute to the phenotypic variations between different ethnic/racial groups.

 
Keywords: 600 mitochondria • 539 genetics • 701 retinal pigment epithelium  
© 2014, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×
This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.Accept