The influence of one-carbon metabolism gene polymorphisms and gene-environment interactions on homocysteine, Vitamin B12, folate and lipids in a Brazilian adolescent population

Abstract

Background: Several single-nucleotide polymorphisms (SNPs) have been associated with the metabolism of Vitamin B12, folic acid, homocysteine and lipids. However, the interaction between SNPs involved in the one-carbon metabolism pathway and macronutrient intake on cardiovascular risk factors in the Brazilian population has not yet been investigated. Hence, the present study examined whether the association of ten SNPs involved in the one-carbon metabolism pathway with Vitamin B12, folic acid, homocysteine and lipid levels is modified by dietary factors and physical activity in adolescents with cardiovascular risk. Materials and Methods: A total of 113 adolescents (10–19 years old), from a public school in the city of Goiânia, Goias, Brazil, underwent anthropometric, biochemical and food consumption evaluations and genetic tests. Results: After adjusting for potential confounders, SNPs rs4633 (catechol-O-methyltransferase, COMT), rs602662 (fucosyltransferase 2, FUT2) and rs1801394 (5-methyltetrahydrofolate-homocysteine methyltransferase reductase) showed significant associations with folic acid (P = 0.042), Vitamin B12 (P = 0.009) and oxidised low-density lipoprotein (ox-LDL) (P = 0.041) concentrations, respectively. The COMT SNP rs4680 showed a significant interaction with carbohydrate intake on ox-LDL concentrations (Pinteraction = 0.005). In addition, the FUT2 SNP rs602662 showed a significant interaction with protein intake on homocysteine concentrations (Pinteraction = 0.007). However, after correction for multiple testing, none of these associations and interactions were statistically significant. Conclusions: For the first time, we provide evidence for the interactions between COMT SNP rs4680 and carbohydrate intake on ox-LDL levels and the FUT2 SNP rs602662 and protein intake on homocysteine concentrations. However, replication of our results in a larger sample size is required to confirm our findings.