engleski

Methylation of CpG islands in HNF1α promoter region affects N-glycan levels in human plasma

Our recent study of variability of plasma glycans in a human population has revealed that the median difference between minimal and maximal levels of individual plasma glycan levels is over six-fold, much more than in any other classes of macromolecules. A large part of this variability appears to be under genetic control since all measured environmental and lifestyle factors explained less than 5% of the variance in the majority of studied glycans, and the composition of the individual plasma glycome was found to be very stable. Contrary to proteins, which are defined by a single gene, glycans are encoded in a complex dynamic network of hundreds of genes that code for proteins involved in the synthesis of glycans. Inter-individual variations in level of plasma glycans can be explained either by genetic polymorphisms, or by epigenetic variations. Recently we identified that polymorphisms (SNPs) in HNF1α significantly affect plasma glycan levels. By performing pyrosequencing of bisulfate converted HNF1α promoter region we determined CpG methylation in leukocyte DNA of 300 individuals from the Croatian island Korčula. Variation in CpG methylation were found to significantly correlate with several features of the plasma glycome, suggesting that epigenetic regulation of HNF1α expression can be important for the regulation of plasma protein N-glycosylation.

bisulphite sequencing; HNF1A; DNA methylation; N-glycosylation; transcription factor

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