title: PRKCZ methylation is associated with sunlight exposure in a North American but not a Mediterranean population.
abstract: 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 461,281 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.
authors: Department of Epidemiology, University of Alabama at Birmingham , Birmingham, AL , USA .
authors: Stella
authors: S
authors: Aslibekyan
authors: Hassan S
authors: HS
authors: Dashti
authors: Toshiko
authors: T
authors: Tanaka
authors: Jin
authors: J
authors: Sha
authors: Luigi
authors: L
authors: Ferrucci
authors: Degui
authors: D
authors: Zhi
authors: Stefania
authors: S
authors: Bandinelli
authors: Ingrid B
authors: IB
authors: Borecki
authors: Devin M
authors: DM
authors: Absher
authors: Donna K
authors: DK
authors: Arnett
authors: Jose M
authors: JM
authors: Ordovas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002940:Circadian Rhythm / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America / Q000208:ethnology; D011493:Protein Kinase C / Q000235:genetics*; D013472:Sunlight; D000099221:Protein Kinase C zeta
chemical_list: D011493:Protein Kinase C; D000099221:Protein Kinase C zeta
keywords: Epigenetics; methylation; protein kinase C; sunlight