Poster Presentation Epigenetics 2013

Circulating miRNAs (155, 15a and 182) correlate with blood folate in an MTHFR genotype dependent manner (#103)

Emma L Beckett 1 2 , Charlotte Martin 2 , Konsta Duesing 1 , Zoe Yates 3 , Martin Veysey 4 , Mark Lucock 2
  1. Animal, Food and Health Sciences, CSIRO , North Ryde, NSW, Australia
  2. Human Molecular Nutrition, University of Newcastle, Ourimbah, NSW, Australia
  3. Biomedical Sciences and Pharmacy, University of Newcastle, Ourimbah, NSW, Australia
  4. Teaching and Research Unit, Central Coast Local Health District, Gosford, NSW, Australia

Nutrition is an important modifiable determinant of epigenetic status. Folate is a particularly important micronutrient, as it is a major source of methyl groups for DNA methylation.1  DNA methylation status can regulate gene expression directly or indirectly via methylation of microRNA gene loci, and therefore the modulation of microRNA levels2 . Circulating miRNAs can be markers of underlying pathological processes3 . Importantly, modulation of epigenetic marks may vary dependent on the underlying genome, particularly due to polymorphisms in genes involved in nutrient metabolism4 .

A preliminary study (n=200) examined the expression of a group of microRNAs potentially regulated by folate levels or methylation status, in plasma, using RT-qPCR. Three microRNAs (miR-155-5p, -15a-5p and -182-5p) were found to significantly inversely correlate with levels of erythrocyte folate (r= -0.13, -0.16 and -0.14, respectively, p<0.05). miR-155-5p and miR-182-5p also negatively correlated with serum folate levels. miR-155 is an oncoMiR5 , miR-15a is a potential tumour suppressor microRNA6 and miR-182 is known to target multiple genes involved in DNA repair pathways7 .

Methylenetetrahydrofolate reductase (MTHFR)is an important enzyme in one carbon metabolism1 . Genotyping was conducted for two common variants of the MTHFR gene (C677T and A1298C) and analyses repeated stratified by genotype. The negative correlations between microRNA expression (miR-155-5p, 15a-5p and -182-5p) and erythrocyte folate were significantly stronger (z=1.97, 2.18, 2.04, respectively, p<0.05) in those possessing the A1298C mutant variant (AC or CC genotype; n=111; r= -0.23, -0.25 and -0.24, respectively, p<0.05) than those possessing the wild-type (AA genotype; n=89; r=0.04, 0.06 and 0.05, respectively, NS). Similar relationships were found for serum folate. C677T genotype did not influence the relationships.

This study demonstrates that circulating levels of microRNAs may correlate with blood levels of folate, potentially via the modulation of methylation status. However, this relationship varies with MTHFR genotype. This highlights the potential importance of the interactions between nutritional and genetic status in influencing the epigenome, and therefore possibly clinically relevant phenotypes.  

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