PRKCZ methylation is associated with sunlight exposure in a North American but not a Mediterranean population

Stella Aslibekyan, Hassan S. Dashti, Toshiko Tanaka, Jin Sha, Luigi Ferrucci, Degui Zhi, Stefania Bandinelli, Ingrid B. Borecki, Devin M. Absher, Donna K. Arnett, Jose M. Ordovas

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Sunlight exposure has been shown to alter DNA methylation patterns across several human cell-types, including T-lymphocytes. Since epigenetic changes establish gene expression profiles, changes in DNA methylation induced by sunlight exposure warrant investigation. The purpose of this study was to assess the effects of sunlight exposure on CD4+ T-cell methylation patterns on an epigenome-wide scale in a North American population of European origin (n=991). In addition, we investigated the genetic contribution to epigenetic variation (methylQTL). We used linear regression to test the associations between methylation scores at 461281 cytosine-phosphate-guanine (CpG) sites and sunlight exposure, followed by a genome-wide association analysis (methylQTL) to test for associations between methylation at the top CpG locus and common genetic variants, assuming an additive genetic model. We observed an epigenome-wide significant association between sunlight exposure and methylation status at cg26930596 (p=9.2×10-8), a CpG site located in protein kinase C zeta (PRKCZ), a gene previously shown to be entrained by light. MethylQTL analysis resulted in significant associations between cg26930596 and two intergenic single nucleotide polymorphisms on chromosome 3, rs4574216 (p=1.5×10-10) and rs4405858 (p=1.9×10-9). These common genetic variants reside downstream of WWTR1, a transcriptional co-Activator of PRKCZ. Associations observed in the North American population, however, did not replicate in an independent Mediterranean cohort. Our preliminary results support the role of sunlight exposure in epigenetic processes, and lay the groundwork for future studies of the molecular link between sunlight and physiologic processes such as tumorigenesis and metabolism.

Original languageEnglish
Pages (from-to)1034-1040
Number of pages7
JournalChronobiology International
Issue number9
StatePublished - Nov 1 2014

Bibliographical note

Funding Information:
The work on the GOLDN study has been funded by the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI), grant U01HL072524-04. The InCHIANTI study baseline (1998–2000) was supported as a ‘‘targeted project’’ (ICS110.1/RF97.71) by the Italian Ministry of Health and, in part, by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336).

Publisher Copyright:
© 2014 Informa Healthcare USA, Inc. All rights reserved.


  • Epigenetics
  • Methylation
  • Protein kinase C
  • Sunlight

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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