correlation of global and gene-specific dna methylation in maternal-infant pairs相关的全球和gene-specific dna甲基化在母婴双.pdf

Correlation of Global and Gene-Specific DNA Methylation in Maternal-Infant Pairs 1 1,2 2 1 1 Molly L. Kile *, Andrea Baccarelli , Letizia Tarantini , Elaine Hoffman , Robert O. Wright , David C. Christiani1 1 Environmental Health Department, Harvard School of Public Health, Boston, Massachusetts, United States of America, 2 Department of Environmental and Occupational Health, Center of Molecular and Genetic Epidemiology, Ca’ Granda Ospedale Maggiore Policlinico IRCCS Foundation, University of Milan, Milan, Italy Abstract The inheritance of DNA methylation patterns is a popular theory to explain the influence of parental genetic and environmental factors on the phenotype of their offspring but few studies have examined this relationship in humans. Using 120 paired maternal-umbilical cord blood samples randomly selected from a prospective birth cohort in Bangladesh, we quantified DNA methylation by pyrosequencing seven CpG positions in the promoter region of p16, four CpG positions in the promoter region of p53, LINE-1 and Alu. Positive correlations were observed between maternal and umbilical cord blood at p16, LINE-1, and Alu but not p53. Multiple linear regression models observed a significant association between maternal and umbilical cord blood at LINE-1 and Alu (LINE-1: b = 0.63, p,0.0001; Alu: b = 0.28, p = 0.009). After adjusting for multiple comparisons, maternal methylation of p16 at position 4 significantly predicted methylation at the same position in umbilical cord blood (b = 0.43, p = ,0.0001). These models explained 48%, 5% and 16% of the observed variability in umbilical cord %5mC for LINE-1, Alu and p16 at position 4, respectively. These results suggest that DNA methylation in maternal