Biosynthesis of U-~(15)Nlabeled deoxycytosine and methyldeoxycytosine for use as internal standards for determining percentage DNA methylation by LC-MS/MS

摘要

CpG islands are deoxycytosine-deoxyguanine rich regions of DNA. These regions are transcription factor binding sites, and are thus important regulation sites for the initiation of transcription. Deoxycytosine methylation in these regions plays an important role in regulating gene transcription, either by directly inhibiting transcription factor binding or by initiating chromatin formation. DNA hypomethylation may also contribute to an increased incidence of strand breakage that leads to chromosomal instability. DNA hypomethylation is inversely related to folate nutritional status, but only in subjects homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677 C->T polymorphism. The TT-genotype is associated with an increased risk of having a child with a neural tube defect (NTD) and is a risk factor for breast, cervical and some colon cancers, particularly in subjects with low folate status. Consequently, it has been speculated that the increased health risk associated with the MTHFR 677TT genotype may, in part, be due to the DNA hypomethylation associated with this genotype.