Plasma S-adenosylmethionine, DNMT polymorphisms, and peripheral blood LINE-1 methylation among healthy Chinese adults in Singapore
1 Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, USA
2 Masonic Cancer Center, University of Minnesota, Minneapolis, USA
3 Department of Epidemiology and Biostatistics, George Washington University, Washington, USA
4 Institute of Metabolic Disease, Baylor Research Institute, Dallas, USA
5 Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
6 Duke-NUS Graduate Medical School, Singapore, Singapore
7 Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, USA
8 Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, USA
BMC Cancer 2013, 13:389 doi:10.1186/1471-2407-13-389Published: 17 August 2013
Global hypomethylation of repetitive DNA sequences is believed to occur early in tumorigenesis. There is a great interest in identifying factors that contribute to global DNA hypomethylation and associated cancer risk. We tested the hypothesis that plasma S-adenosylmethionine (SAM) level alone or in combination with genetic variation in DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) was associated with global DNA methylation extent at long interspersed nucleotide element-1 (LINE-1) sequences.
Plasma SAM level and LINE-1 DNA methylation index were measured using stored blood samples collected from 440 healthy Singaporean Chinese adults during 1994-1999. Genetic polymorphisms of 13 loci in DNMT1, DNMT3A and DNMT3B were determined.
LINE-1 methylation index was significantly higher in men than in women (p = 0.001). LINE-1 methylation index was positively associated with plasma SAM levels (p ≤ 0.01), with a plateau at approximately 78% of LINE-1 methylation index (55 nmol/L plasma SAM) in men and 77% methylation index (50 nmol/L plasma SAM) in women. In men only, the T allele of DNMT1 rs21124724 was associated with a statistically significantly higher LINE-1 methylation index (ptrend = 0.001). The DNMT1 rs2114724 genotype modified the association between plasma SAM and LINE-1 methylation index at low levels of plasma SAM in men.
Circulating SAM level was associated with LINE-1 methylation status among healthy Chinese adults. The DNMT1 genetic polymorphism may exert a modifying effect on the association between SAM and LINE-1 methylation status in men, especially when plasma SAM level is low. Our findings support a link between plasma SAM and global DNA methylation status at LINE-1 sequences.