title: Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis.
abstract: BACKGROUND
  Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals.
  
  
  METHODS
  Individual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing.
  
  
  RESULTS
  Age [β = -0.011% of 5-methyl-cytosine (%5 mC)/year, 95% confidence interval (CI) -0.020 to -0.001%5 mC/year] and alcohol drinking (β = -0.214, 95% CI -0.415 to -0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (β = -0.385, 95% CI -0.665 to -0.104) and higher LINE-1 methylation (β = 0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (β = 0.036, 95% CI 0.010 to 0.061) and negative (β = -0.038, 95% CI -0.065 to -0.012) association with LINE-1 methylation, respectively.
  
  
  CONCLUSIONS
  Global methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes.
authors.affiliation: Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy.
authors.forename: Zhong-Zheng
authors.initials: ZZ
authors.lastname: Zhu
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.forename: Barbara
authors.initials: B
authors.lastname: Marinelli
authors.forename: Laura
authors.initials: L
authors.lastname: Cantone
authors.forename: Allen S
authors.initials: AS
authors.lastname: Yang
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Silvia
authors.initials: S
authors.lastname: Fustinoni
authors.forename: Angela C
authors.initials: AC
authors.lastname: Pesatori
authors.forename: Matteo
authors.initials: M
authors.lastname: Bonzini
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Costa
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D020087:Alu Elements / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D055815:Young Adult
chemical_list: D004247:DNA