Association of Polymorphisms in Genes Involved in One-Carbon Metabolism with MTHFR Methylation Levels

• Published in: International journal of molecular sciences Vol. 20; no. 15; p. 3754
• Main Authors: Coppedè, Fabio, Stoccoro, Andrea, Tannorella, Pierpaola, Gallo, Roberta, Nicolì, Vanessa, Migliore, Lucia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.07.2019; MDPI
• Subjects: 5-Methyltetrahydrofolate-homocysteine S-methyltransferase; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - metabolism; Aged; Aged, 80 and over; Blood; Carbon; Cardiovascular disease; Colorectal cancer; Communication; Congenital diseases; Deoxyribonucleic acid; DNA; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA Methylation; DNA Methyltransferase 3A; DNA Methyltransferase 3B; DNMT3B; DNMT3B gene; Down syndrome; Enzymes; Epigenesis, Genetic; epigenetics; Female; Ferredoxin-NADP Reductase - genetics; Ferredoxin-NADP Reductase - metabolism; folate metabolism; Folic acid; Folic Acid - metabolism; Gene expression; Gene polymorphism; Genes; Genetic testing; Genotype; Haplotypes; Healthy Volunteers; Homocysteine; Humans; Infertility; Male; Metabolic Networks and Pathways - genetics; Metabolism; Methionine; Methionine - metabolism; methylation; Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; Middle Aged; Miscarriage; MTHFR; one-carbon metabolism; Pancreatic cancer; Polymorphism; Polymorphism, Single Nucleotide; polymorphisms; Reduced Folate Carrier Protein - genetics; Reduced Folate Carrier Protein - metabolism; Reductases; Studies; Tetrahydrofolic acid; Thymidylate Synthase - genetics; Thymidylate Synthase - metabolism; Tumor suppressor genes; Vitamin B; methylenetetrahydrofolate reductase; methylation; DNMT3B; MTHFR; folate metabolism; polymorphisms; epigenetics; one-carbon metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20153754

Methylenetetrahydrofolate reductase (MTHFR) is a pivotal enzyme in the one-carbon metabolism, a metabolic pathway required for DNA synthesis and methylation reactions. hypermethylation, resulting in reduced gene expression, can contribute to several human disorders, but little is still known about the factors that regulate methylation levels. We performed the present study to investigate if common polymorphisms in one-carbon metabolism genes contribute to methylation levels. methylation was assessed in peripheral blood DNA samples from 206 healthy subjects with methylation-sensitive high-resolution melting (MS-HRM); genotyping was performed for 677C>T (rs1801133) and 1298A>C (rs1801131), 66A>G (rs1801394), 2756A>G (rs1805087), ( ) 80G>A (rs1051266), 28-bp tandem repeats (rs34743033) and 1494 6-bp ins/del (rs34489327), -448A>G (rs1550117), and -149C>T (rs2424913) polymorphisms. We observed a statistically significant effect of the -149C>T polymorphism on mean methylation levels, and particularly CT and TT carriers showed increased methylation levels than CC carriers. The present study revealed an association between a functional polymorphism of and methylation levels that could be of relevance in those disorders, such as inborn defects, metabolic disorders and cancer, that have been linked to impaired DNA methylation.