Aberrant leukocyte telomere length in Birdshot Uveitis

Nadia Vazirpanah, Fleurieke H Verhagen, Anna Rothova, Tom O A R Missotten, Mirjam van Velthoven, Anneke I Den Hollander, Carel B Hoyng, Timothy R D J Radstake, Jasper C A Broen, Jonas J W Kuiper

Research output: Contribution to journalArticleResearchpeer-review

Abstract

PURPOSE: Birdshot Uveitis (BU) is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.

METHODS: To study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL) in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls.

RESULTS: Although LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL) = 4.87 (= 74131 base pair) compared to 4.31 (= 20417 base pair) in unaffected controls (P<0.0001). The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1.

CONCLUSIONS: These findings suggest that BU is accompanied by significantly longer LTL.

Original languageEnglish
Pages (from-to)e0176175
JournalPLoS ONE
Volume12
Issue number5
DOIs
Publication statusPublished - 2017

Keywords

  • Female
  • Gene Expression
  • Genetic Predisposition to Disease
  • Humans
  • Leukocytes/immunology
  • Male
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Telomerase/metabolism
  • Telomere/metabolism
  • Telomere Homeostasis
  • Telomere Shortening
  • Uveitis/genetics

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