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The MTHFR 677TT Variant is Associated with Impaired Acute Blood Pressure Response to Sodium Ingestion
Author(s) -
Murphy Melissa A,
Breslin Paul A S,
Miller Joshua W
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.802.30
Subject(s) - methylenetetrahydrofolate reductase , ingestion , blood pressure , medicine , sodium , endocrinology , genotype , chemistry , biochemistry , organic chemistry , gene
Observational and genome‐wide association studies indicate that a common polymorphism (677C‐‐>T) in the FAD‐dependent enzyme, methylenetetrahydrofolate reductase (MTHFR), is associated with elevated blood pressure (BP) and increased risk of hypertension. This association is modified by riboflavin status and riboflavin supplements reduce BP in individuals homozygous for the variant form of the enzyme (677TT). However, little is known about the effect of the 677TT variant on dynamic responses of BP to vaso reactive stimuli. Previously, we demonstrated that systolic BP (SBP) drops in healthy adults within one hour after ingestion of a sodium chloride (NaCl) solution. To determine if MTHFR genotype impacts this acute BP response to NaCl ingestion, we tested 20 normotensive individuals (age 18–35y), 9 with the 677TT variant and 11 wild‐type controls (677CC) in a repeated measures design. On 6 different days, BP was measured in the subjects in the sitting position with a mercury brachial sphygmomanometer every 10 minutes for 60 minutes post ingestion of 475 mL of either a 157 mM NaCl solution or water with no NaCl. Plasma riboflavin was determined by HPLC. In all subjects there was an average of 3.1 ± 2.7 mmHg greater drop in SBP after ingesting the NaCl solution compared with water alone (p = 0.018). Additionally, the decrease in SBP was greater for 677CC individuals compared with 677TT individuals in both conditions: 677CC‐NaCl = −8.18 ± 3.62 mmHg vs. 677TT‐NaCl = −6.59 ± 2.15 mmHg and 677CC‐Water = −6.94 ± 2.01 mmHg vs. 677TT‐Water = −5.37 ± 2.78 mmHg (p = 0.013). Plasma riboflavin was not different between the 677CC and 677TT groups (14.4 ± 8.8 vs. 17.2 ± 11.9 nmol/L, respectively). These data indicate a lesser SBP response to NaCl ingestion, independent of riboflavin status, in the 677TT group, suggesting that acute regulation of BP in response to a vasoreactive stimulus may be impaired as a result of this gene variant. Support or Funding Information NIH DC02995