Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis.
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.
Zhu
Zhong-Zheng
ZZ
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.
Hou
Lifang
L
Bollati
Valentina
V
Tarantini
Letizia
L
Marinelli
Barbara
B
Cantone
Laura
L
Yang
Allen S
AS
Vokonas
Pantel
P
Lissowska
Jolanta
J
Fustinoni
Silvia
S
Pesatori
Angela C
AC
Bonzini
Matteo
M
Apostoli
Pietro
P
Costa
Giovanni
G
Bertazzi
Pier Alberto
PA
Chow
Wong-Ho
WH
Schwartz
Joel
J
Baccarelli
Andrea
A
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
D004247:DNA