title: Gene promoter methylation and DNA repair capacity in monozygotic twins with discordant smoking habits.
abstract: The influence of DNA repair capacity, plasma nutrients and tobacco smoke exposure on DNA methylation was investigated in blood cells of twenty-one couples of monozygotic twins with discordant smoking habits. All study subjects had previously been characterized for mutagen sensitivity with challenge assays with ionizing radiation in peripheral blood lymphocytes. Plasma levels of folic acid, vitamin B12 and homocysteine were also available from a previous investigation. In this work DNA methylation in the promoter region of a panel of ten genes involved in cell cycle control, differentiation, apoptosis and DNA repair (p16, FHIT, RAR, CDH1, DAPK1, hTERT, RASSF1A, MGMT, BRCA1 and PALB2) was assessed in the same batches of cells isolated for previous studies, using the methylation-sensitive high-resolution melting technique. Fairly similar profiles of gene promoter methylation were observed within co-twins compared to unrelated subjects (p= 1.23 × 10(-7)), with no significant difference related to smoking habits (p = 0.23). In a regression analysis the methylation index of study subjects, used as synthetic descriptor of overall promoter methylation, displayed a significant inverse correlation with radiation-induced micronuclei (p = 0.021) and plasma folic acid level (p = 0.007) both in smokers and in non-smokers. The observed association between repair of radiation-induced DNA damage and promoter methylation suggests the involvement of the DNA repair machinery in DNA modification. Data also highlight the possible modulating effect of folate deficiency on DNA methylation and the strong influence of familiarity on the individual epigenetic profile.
authors: Department of Molecular Medicine, University of Rome, La Sapienza, Rome, Italy.
authors: Laura
authors: L
authors: Ottini
authors: Department of Molecular Medicine, University of Rome, La Sapienza, Rome, Italy.
authors: Piera
authors: P
authors: Rizzolo
authors: Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
authors: Ester
authors: E
authors: Siniscalchi
authors: Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
authors: Andrea
authors: A
authors: Zijno
authors: Department of Molecular Medicine, University of Rome, La Sapienza, Rome, Italy.
authors: Valentina
authors: V
authors: Silvestri
authors: Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy. Electronic address: riccardo.crebelli@iss.it.
authors: Riccardo
authors: R
authors: Crebelli
authors: Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
authors: Francesca
authors: F
authors: Marcon
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D004260:DNA Repair; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008019:Life Style; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000235:genetics*; D014430:Twins, Monozygotic; D014805:Vitamin B 12 / Q000097:blood; D055815:Young Adult
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: DNA methylation; DNA repair capacity; Folic acid; Tobacco smoke; Twins