MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is a critical folate-metabolising enzyme which requires riboflavin as its co-factor. A common polymorphism (677C→T) in the MTHFR gene results in reduced MTHFR activity in vivo which in turn leads to impaired folate metabolism and elevated homocysteine concentrations. Homozygosity for this polymorphism (TT genotype) is associated with an increased risk of a number of conditions including heart disease and stroke, but there is considerable variability in the extent of excess risk in various reports. The present review will explore the evidence which supports a role for this polymorphism as a risk factor for a number of adverse health outcomes, and the potential modulating roles for B-vitamins in alleviating disease risk. The evidence is convincing in the case which links this polymorphism with hypertension and hypertensive disorders of pregnancy, particularly preeclampsia. Furthermore, elevated blood pressure was found to be highly responsive to riboflavin intervention specifically in individuals with the MTHFR 677TT genotype. Future intervention studies targeted at these genetically predisposed individuals are required to further investigate this novel gene–nutrient interaction. This polymorphism has also been associated with an increased risk of neural tube defects (NTD) and other adverse pregnancy outcomes; however, the evidence in this area has been inconsistent. Preliminary evidence has suggested that there may be a much greater need for women with the MTHFR 677TT genotype to adhere to the specific recommendation of commencing folic acid prior to conception for the prevention of NTD, but this requires further investigation.

Interactions between lifestyle and MTHFR polymorphisms on homocysteine concentrations in young adults belonging to the 1982 Pelotas Birth Cohort

“…Also, the lack of measurements of vitamins should be mentioned, especially riboflavin, which has been described as an important nutrient that influences disease risk associated with the MTHFR C677T polymorphism. 13 Furthermore, we do not have information about supplement use in the 22-23-year follow-up. Finally, we did not analyze different types of alcoholic beverages.…”

“…9,10 Hcy concentrations depend on age, sex and lifestyle variables, such as smoking, alcohol intake, physical activity and nutritional status, especially related to folate and vitamin B deficiencies. 2,4,11,12 As recently discussed by Reilly et al, 13 on the basis of a meta-analysis of randomized trials, a reduction in Hcy concentrations by approximately 25% was demonstrated after supplementation with folic acid, the synthetic form of folate. In addition, single-nucleotide polymorphisms (SNPs) that have an impact on Hcy concentrations are described.…”

Recent genetic discoveries in osteoporosis, sarcopenia and obesity [Review]

“…1). Methylenetetrahydrofolate reductase (MTHFR), an important enzyme in the methionine cycle [57], is involved in the removal of circulating homocysteine. MTHFR lies within a linkage region on chromosome 1p36 that is associated with the regulation of BMD [58,59].…”

“…A C677T nonsynonymous and functional polymorphism has been identified in exon 4 of MTHFR that results in an alanine to valine change. The T-allele variant (valine type) has a lower MTHFR activity than the wild type (C-allele or alanine type) and is also associated with moderately elevated homocysteine levels [57]. An elevated homocysteine level has been recognized as a significant risk factor for fractures [60][61][62], independent of age and BMD, because it is caused by abnormal collagen cross-links during bone calcification [63][64][65].…”

Valores séricos de ácido fólico en un grupo de pacientes mayores de 18 años de edad en un hospital de alta complejidad

“…Se encuentra en alimentos como las verduras de hoja verde, legumbres, frutos secos y granos enteros como las almendras [2]. El ácido fólico es de particular interés clínico por su relación con la anemia megaloblástica y diversos trastornos neurológicos relacionados con la carencia de la vitamina [3,4], suplencia perinatal y prevención de defectos del tubo neural [5], metabolismo de la homocisteína y su asociación con eventos vasculares cardiacos y cerebrales [6] y su relación con la disminución del riesgo a padecer diversos tipos de cáncer [7].…”