title: Methylation at global LINE-1 repeats in human blood are affected by gender but not by age or natural hormone cycles.
abstract: Previously, we reported on inter-individual and gender specific variations of LINE-1 methylation in healthy individuals. In this study, we investigated whether this variability could be influenced by age or sex hormones in humans. To this end, we studied LINE-1 methylation in vivo in blood-derived DNA from individuals aged 18 to 64 years and from young healthy females at various hormone levels during the menstrual cycle. Our results show that no significant association with age was observed. However, the previously reported increase of LINE-1 methylation in males was reconfirmed. In females, although no correlation between LINE-1 or Alu methylation and hormone levels was observed, a significant stable individual specific level of methylation was noted. In vitro results largely confirmed these findings, as neither estrogen nor dihydrotestosterone affected LINE-1 or Alu methylation in Hek293T, HUVEC, or MDA-kb2 cell lines. In contrast, a decrease in methylation was observed in estrogen-treated T47-Kbluc cell lines strongly expressing estrogen receptor. The very low expression of estrogen receptor in blood cells could explain the observed insensitivity of methylation at LINE-1 to natural hormonal variations in females. In conclusion, neither natural cycle of hormones nor age has a detectable effect on the LINE-1 methylation in peripheral blood cells, while gender remains an important factor.
authors.affiliation: Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn, Germany. osman.elmaarri@ukb.uni-bonn.de
authors.forename: Osman
authors.initials: O
authors.lastname: El-Maarri
authors.forename: Maja
authors.initials: M
authors.lastname: Walier
authors.forename: Frank
authors.initials: F
authors.lastname: Behne
authors.forename: Jan
authors.initials: J
authors.lastname: van Üüm
authors.forename: Heike
authors.initials: H
authors.lastname: Singer
authors.forename: Amalia
authors.initials: A
authors.lastname: Diaz-Lacava
authors.forename: Nicole
authors.initials: N
authors.lastname: Nüsgen
authors.forename: Barbara
authors.initials: B
authors.lastname: Niemann
authors.forename: Matthias
authors.initials: M
authors.lastname: Watzka
authors.forename: Jochen
authors.initials: J
authors.lastname: Reinsberg
authors.forename: Hans
authors.initials: H
authors.lastname: van der Ven
authors.forename: Thomas
authors.initials: T
authors.lastname: Wienker
authors.forename: Birgit
authors.initials: B
authors.lastname: Stoffel-Wagner
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwaab
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001769:Blood; D002460:Cell Line; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D012739:Gonadal Steroid Hormones / Q000032:analysis / Q000502:physiology; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis / Q000502:physiology; D012737:Sex Factors; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D011960:Receptors, Estrogen; D004247:DNA