Genetic Variants Involved in One-Carbon Metabolism: Polymorphism Frequencies and Differences in Homocysteine Concentrations in the Folic Acid Fortification Era

Abstract

Folate and other B vitamins are essential co-factors of one-carbon metabolism, and genetic variants, such as polymorphisms, can alter the metabolism. Furthermore, the adoption of food fortification with folic acid showed a decrease of homocysteine concentration. The aim of this study was to investigate the frequencies of the polymorphisms of enzymes and carrier proteins involved in one-carbon metabolism, and to evaluate homocysteine concentrations in the presence of these genetic variants in a population exposed to mandatory food fortification with folic acid. Using data from a population-based cross-sectional study in São Paulo, Brazil, the study population comprised 750 participants above 12 years of age of both genders. A linear regression model was used to evaluate the homocysteine concentrations according to genetic variants and folate level. The results showed that the minor allelic frequencies were 0.33 for MTHFR (rs1801133), 0.24 for MTHFR (rs1801131), 0.19 for MTR (rs1805087), 0.42 for MTRR (rs1801394), 0.46 for RFC1 (rs1051266), and 0.47 for DHFR (19-bp deletion). The genetic variants of MTHFR 677C>T, MTRR 66A>G and RFC-1 80G>A were different according to race. The homocysteine concentrations increased in the CT and TT compared to CC genotypes of polymorphism MTHFR 677C>T in all populations, and differences between the homocysteine concentrations according to the genotypes of MTHFR 677C>T were observed regardless of folate level.

Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism and Infant’s Anthropometry at Birth

“…This reduced catalytic activity of MTHFR declines the production of 5-MTHF from folate. 5-MTHF is the active and circulating form of folate, which is a methyl donor for the conversion of homocysteine to methionine [ 12 , 30 , 31 ]. When methionine is converted back to homocysteine, the methyl group released causes DNA methylation [ 12 ].…”

A nutrigenetics approach to study the impact of genetic and lifestyle factors on cardiometabolic traits in various ethnic groups: findings from the GeNuIne Collaboration

“…Epidemiological studies have shown that hyperhomocysteinaemia is a well-known independent risk factor for atherosclerotic vascular disease and hypercoagulability states (72) . Studies have shown significant interactions between SNP involved in the C 1 metabolism pathway and dietary factors on homocysteine concentrations (73,74) . However, no studies, to date, have examined the interaction between C 1 metabolism-related genes and lifestyle factors on vitamin B 12 , folate and lipid concentrations.…”

“…The global physical activity questionnaire was used to assess physical activity. Ten common SNP involved in the C 1 metabolism pathway were selected based on the published reports (74,76–80) . The study identified significant interactions between the catechol-o-methyl transferase SNP (rs4680 and rs4633) and dietary carbohydrate intake on HDL-cholesterol concentrations ( P = 0·011 and 0·036, respectively).…”

Personalized Nutrition for Management of Micronutrient Deficiency—Literature Review in Non-bariatric Populations and Possible Utility in Bariatric Cohort

“…A common genetic variant in MTHFR is known to influence blood folate and prevalent in 10% of the population worldwide [85,86]. Steluti and colleagues studied polymorphism frequencies and differences in homocysteine concentrations even in the presence of folic acid fortification and found that homocysteine levels increased in those carrying genetic variants in folate metabolism, specifically in the MTHFR gene [87]. The prevalence of variant MTHFR TT has been found in 25% of Americans of Hispanic origin, 10-15% among white Americans, and only 0-1% for African Americans [77,[87][88][89].…”

“…Steluti and colleagues studied polymorphism frequencies and differences in homocysteine concentrations even in the presence of folic acid fortification and found that homocysteine levels increased in those carrying genetic variants in folate metabolism, specifically in the MTHFR gene [87]. The prevalence of variant MTHFR TT has been found in 25% of Americans of Hispanic origin, 10-15% among white Americans, and only 0-1% for African Americans [77,[87][88][89]. A review examining the nutritional deficiencies, bariatric surgery, and serum homocysteine levels found that the mutations of the MTHFR gene can be one of the reasons for persistent elevated serum homocysteine after surgery despite supplementation with B-group vitamins [76].…”