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High ferritin and low folate increases PBMCs genomic DNA methylation in association with SHMT1–1420TT variant
Author(s) -
Moruzzi Sara,
Guarini Patrizia,
Udali Silvia,
Olivieri Oliviero,
Girelli Domenico,
Pattini Patrizia,
Pizzolo Francesca,
Choi Sang Woon,
Friso Simonetta
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.640.14
Subject(s) - dna methylation , epigenetics , ferritin , methylation , peripheral blood mononuclear cell , biology , chemistry , microbiology and biotechnology , genetics , cancer research , gene , biochemistry , gene expression , in vitro
Nutrient‐gene interactions within one‐carbon metabolism modulate DNA methylation, the major potentially reversible epigenetic modification in eukaryotic cells. The cytosolic serine hydroxymethyltransferase (SHMT1) regulates the metabolic balance between nucleotide synthesis and methylation in one‐carbon pathway. The SHMT1–1420T allele has been associated with a reduced enzyme activity and a decreased risk of cancer. By enhancing SHMT1 expression , ferritin affects folate‐mediated one‐carbon metabolism. Aim of this study was to analyze how the interaction among ferritin, folate and SHMT1 ‐ 1420C>;T polymorphism may affect peripheral blood mononuclear cells (PBMCs) DNA methylation (LC/ESI/MS method) in 537 subjects enrolled in the Verona Heart Study to identify a possible biomarker for cancer. Results showed that SHMT1‐TT carriers, under a high ferritin/low folate condition, show significantly increased PBMCs genomic DNA methylation than SHMT1‐CC subjects ( P =0.01). Since cancer is usually associated with genomic hypomethylation, the increased genomic methylation in SHMT1–1420TT genotypes in presence of high ferritin/low folate, could be potentially protective for cancer risk.