Background: Global hypomethylation of repetitive DNA sequences is believed to occur early in tumorigenesis.\r\nThere is a great interest in identifying factors that contribute to global DNA hypomethylation and associated cancer\r\nrisk. We tested the hypothesis that plasma S-adenosylmethionine (SAM) level alone or in combination with genetic\r\nvariation in DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) was associated with global DNA methylation\r\nextent at long interspersed nucleotide element-1 (LINE-1) sequences.\r\nMethods: Plasma SAM level and LINE-1 DNA methylation index were measured using stored blood samples\r\ncollected from 440 healthy Singaporean Chinese adults during 1994-1999. Genetic polymorphisms of 13 loci in\r\nDNMT1, DNMT3A and DNMT3B were determined.\r\nResults: LINE-1 methylation index was significantly higher in men than in women (p = 0.001). LINE-1 methylation\r\nindex was positively associated with plasma SAM levels (p = 0.01), with a plateau at approximately 78% of LINE-1\r\nmethylation index (55 nmol/L plasma SAM) in men and 77% methylation index (50 nmol/L plasma SAM) in women.\r\nIn men only, the T allele of DNMT1 rs21124724 was associated with a statistically significantly higher LINE-1\r\nmethylation index (ptrend = 0.001). The DNMT1 rs2114724 genotype modified the association between plasma SAM\r\nand LINE-1 methylation index at low levels of plasma SAM in men.\r\nConclusions: Circulating SAM level was associated with LINE-1 methylation status among healthy Chinese adults.\r\nThe DNMT1 genetic polymorphism may exert a modifying effect on the association between SAM and LINE-1\r\nmethylation status in men, especially when plasma SAM level is low. Our findings support a link between plasma\r\nSAM and global DNA methylation status at LINE-1 sequences.
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