The MTHFR C677T polymorphism and riboflavin : a novel gene-nutrient interaction affecting blood pressure

Hypertension IS a major risk factor for CVD and unequivocal evidence has demonstrated a continuous and linear relationship between elevated blood pressure (BP) and stroke. Among the many established risk factors for hypertension, a novel gene- nutrient interaction with a potential role in BP has recently emerged. A common polymorphism (677C---)oT) in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) produces a variant enzyme with decreased activity, and recent work at this centre in premature CVD patients reported that stabilisation of the variant enzyme by administration of its cofactor riboflavin may lower BP. The aim of this thesis was to further investigate the association between the MTHFR 677C---)o T polymorphism and BP and to evaluate the potential modulating role of riboflavin. The findings of this thesis demonstrated that riboflavin supplementation at the dietary level (1.6mg/dI16weeks) produced a genotype-specific lowering of BP that was clinically significant and that this effect was not confined solely to high-risk CVD patients but may in fact be applicable to hypertensive patients generally with the TT genotype. Preliminary work using 24-hour ambulatory blood pressure monitoring (ABPM) reported a non-significant trend towards higher BP in those with the TT genotype compared to those with the CC and CT genotypes. It also appeared to suggest that MTHFR genotype may have an effect on nocturnal BP characterised by non- dipping status, itself a cardiovascular risk factor independently of 24-hour blood pressure. In conclusion this thesis has confirmed that the MTHFR 677 TT genotype is a risk factor for hypertension and that optimisation of riboflavin status offers a targeted nutritional therapy with clinically relevant effects on BP specifically in this genotype group. Given the frequency of this polymorphism worldwide and the global burden of blood pressure-related disease, these findings could have important public health implications.EThOS - Electronic Theses Online ServiceGBUnited Kingdo