June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Differential Expression of Wnt Genes in Transmitochondrial Cybridswith African-origin versus European-origin mtDNA
Author Affiliations & Notes
  • Rodrigo Donato Costa
    Ophthalmology, University of California Irvine, Irvine, CA
    Retina, Instituto Donato Oftalmologia, Poços de Caldas, Brazil
  • Javier Cáceres-del-Carpio
    Ophthalmology, University of California Irvine, Irvine, CA
  • Sonali R Nashine
    Ophthalmology, University of California Irvine, Irvine, CA
  • Young Gyun Kim
    Ophthalmology, University of California Irvine, Irvine, CA
    Ophthalmology, Eulji University, Seoul, Korea (the Republic of)
  • Deepika Malik
    Ophthalmology, University of California Irvine, Irvine, CA
  • Carolina Yañez
    Ophthalmology, University of California Irvine, Irvine, CA
  • Kunal Thaker
    Ophthalmology, University of California Irvine, Irvine, CA
  • Tej Patel
    Ophthalmology, University of California Irvine, Irvine, CA
  • Baruch Kuppermann
    Ophthalmology, University of California Irvine, Irvine, CA
  • Cristina M Kenney
    Ophthalmology, University of California Irvine, Irvine, CA
  • Footnotes
    Commercial Relationships Rodrigo Costa, None; Javier Cáceres-del-Carpio, None; Sonali Nashine, None; Young Gyun Kim, None; Deepika Malik, None; Carolina Yañez, None; Kunal Thaker, None; Tej Patel, None; Baruch Kuppermann, AcuFocus (C), Alcon (C), Alimera (C), Allegro (C), Allergan (C), Ampio (C), Aqua Therapeutics (C), Bausch&Lomb (C), Genentech (C), GSK (C), Neurotech (C), Novagalli (C), Novartis (C), Ophthotech (C), Regeneron (C), Regeneron (C), SecondSight (C), Staar Surgical (C), Teva (C), ThromboGenics (C); Cristina Kenney, Allergan (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 828. doi:
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      Rodrigo Donato Costa, Javier Cáceres-del-Carpio, Sonali R Nashine, Young Gyun Kim, Deepika Malik, Carolina Yañez, Kunal Thaker, Tej Patel, Baruch Kuppermann, Cristina M Kenney; Differential Expression of Wnt Genes in Transmitochondrial Cybridswith African-origin versus European-origin mtDNA . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):828.

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

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Abstract
 
Purpose
 

In the United States approximately 11% of all African-Americans, older than 20 years, have diabetes. Diabetes is a disease of metabolism and mitochondria (mt) play a key role. Human mtDNA can be categorized into haplogroups which are polymorphisms inherited along maternal lineages and define geographic origins of human populations. The most common European haplogroup is H and maternal African-origin haplogroup is L. The canonical Wnt pathway plays a key role in development of retinal vasculature and diabetic retinopathy. This study uses transmitochondrial cybrids to determine if L versus H haplogroups influence expression patterns of diabetes-associated genes.

 
Methods
 

Cybrid cell lines were established by fusing mitochondria-deficient human ARPE-19 cells with platelets from individuals of either European-origin (H, n=6) or African-origin L, n=8). Cybrids were cultured, RNA was extracted from each cybrid and cDNA synthesized. Q-PCR was performed using primers for genes associated with the Wnt pathway (DDK3, SFRP1, KREMEN1, GSK3A, and RARA1) and glucose metabolism and insulin signaling (RPS6KA4). For statistical analysis, a standard student’s t-test was used to measure the significant differences between gene expression levels using the delta-delta-Ct’s (ddCt) for each gene in L cybrids relative to H cybrids.

 
Results
 

The L cybrids had different expression levels for four Wnt-related genes compared to H cybrids: Expression for two Wnt inhibitors (DDK3, 0.06-fold, p = 0.03; SFRP1, 0.2-fold, p = 0.0035) were decreased while KREMEN1 expression was elevated (1.28-fold, p =0.007). There was an increased level for RPS6KA4, (1.6-fold, p = 0.035). The GSK3A and RARA1 gene expressions in the L cybrids were similar to the H cybrids (0.8-fold, p = 0.06 and 0.95-fold, p = 0.6, respectively).

 
Conclusions
 

Although all cybrids have identical nuclear genes, the expression levels of diabetes-related genes were significantly different in L versus H cybrids. Based upon our findings, we propose that a person’s mtDNA haplogroup background acts as a “modifier” for gene expression in major pathways related to diseases and this contributes to disparities found in diabetes and other ethnic/racial susceptible diseases. In addition, the Wnt pathway may be a potential target for therapy of diabetic retinopathy and other diseases with neovascular pathologies.

 
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