title: Transcriptomic profiling explains racial disparities in pterygium patients treated with doxycycline.
abstract: OBJECTIVE
  To understand the differential responses to doxycycline between Caucasian and Hispanic patients observed in a previous clinical trial.
  
  
  METHODS
  Primary cultures were established using pterygia excised from male Caucasian (n = 3) and Hispanic (n = 6) patients. The response of these cells to doxycycline was tested in a toxicity assay. In addition, a complete transcriptome was obtained from the nine samples, and the results were analyzed using false discovery rate statistics. Results were confirmed by quantitative RT (qRT)-PCR and Western blotting for a limited set of genes.
  
  
  RESULTS
  Caucasian pterygium cells underwent apoptosis upon exposure to doxycycline, whereas Hispanic cells survived the treatment. Transcriptomic analysis showed profound differences between cells of both ethnicities, even before treatment, implicating important cellular pathways such as the mitochondrial oxidative phosphorylation chain, the proteasome, and the components of the extracellular matrix. Following exposure to doxycycline, there was a significant increase in proapoptotic proteins, regulators of the cell cycle, and components of the mitochondrial membrane in Caucasian cells but not in their Hispanic counterparts. There was a good correlation between data obtained by ultrasequencing and those generated by qRT-PCR or Western blotting.
  
  
  CONCLUSIONS
  The lack of response to doxycycline observed in Hispanic pterygium patients in a previous clinical trial can be explained by the genetic protection afforded to the cells in this ethnic background against apoptosis and cell death. New therapeutic options must be devised for these patients.
authors.affiliation: Oncology Area, Center for Biomedical Research of La Rioja, Logroño, Spain.
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Larrayoz
authors.affiliation: Ophthalmology Service, Hospital San Pedro, Logroño, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Rúa
authors.affiliation: Ophthalmology Service, Hospital San Pedro, Logroño, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Velilla
authors.affiliation: Oncology Area, Center for Biomedical Research of La Rioja, Logroño, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Martínez
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D003228:Conjunctiva / Q000187:drug effects / Q000473:pathology; D004318:Doxycycline / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011625:Pterygium / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D044469:Racial Groups; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013030:Spain / Q000453:epidemiology; D059467:Transcriptome / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D012333:RNA, Messenger; D004318:Doxycycline
keywords: doxycycline; pterygium; racial disparities; transcriptomic analysis