1.
MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment.
Huang, X, Qin, X, Yang, W, Liu, L, Jiang, C, Zhang, X, Jiang, S, Bao, H, Su, H, Li, P, et al
Arteriosclerosis, thrombosis, and vascular biology. 2018;(3):679-685
Abstract
OBJECTIVE This post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial) assessed the individual variation in total homocysteine (tHcy)-lowering response after an average 4.5 years of 0.8 mg daily folic acid therapy in Chinese hypertensive adults and evaluated effect modification by methylenetetrahydrofolate reductase (MTHFR) C677T genotypes and serum folate levels. APPROACH AND RESULTS This analysis included 16 413 participants from the CSPPT, who were randomly assigned to 2 double-blind treatment groups: either 10-mg enalapril+0.8-mg folic acid or 10-mg enalapril, daily and had individual measurements of serum folate and tHcy levels at baseline and exit visits and MTHFR C677T genotypes. Mean baseline tHcy levels were comparable between the 2 treatment groups (14.5±8.5 versus 14.4±8.1 μmol/L; P=0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7±6.1 μmol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4±7.9 μmol/L, group difference: 1.61 μmol/L; 11% reduction). More importantly, tHcy lowering varied by MTHFR genotypes and serum folate levels. Compared with CC and CT genotypes, participants with the TT genotype had a more prominent L-shaped curve between tHcy and serum folate levels and required higher folate levels (at least 15 ng/mL) to eliminate the differences in tHcy by genotypes. CONCLUSIONS Compared with CC or CT, tHcy in the TT group manifested a heightened L-shaped curve from low to high folate levels, but this difference in tHcy by genotype was eliminated when plasma folate levels reach ≈15 ng/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual MTHFR C677T genotype and folate status. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.
2.
[Impact of adding folic acid, vitamin B(12) and probucol to standard antihypertensive medication on plasma homocysteine and asymmetric dimethylarginine levels of essential hypertension patients].
Wu, CJ, Wang, L, Li, X, Wang, CX, Ma, JP, Xia, XS
Zhonghua xin xue guan bing za zhi. 2012;(12):1003-8
Abstract
OBJECTIVE To investigate the impact of adding folic acid, vitamin B(12) and probucol to standard antihypertensive medication on plasma homocysteine (Hcy) and asymmetric dimethylarginine (ADMA), serum NO and eNOS of essential hypertensive patients. METHOD A total of 120 patients with hypertension were randomly divided to three groups (n = 40 each): group 1 (standard medication), group 2 (adding folic acid 5 mg/day and vitamin B(12) 500 µg twice daily) and group 3 (adding folic acid 5 mg/day and vitamin B(12) 500 µg twice daily and probucol 500 mg twice daily). Plasma Hcy and ADMA, serum NO and eNOS levels were observed at baseline, 2 and 12 weeks after various therapy. RESULTS In group 1, concentrations of plasma Hcy [(23.06 ± 14.15) µmol/L, (23.67 ± 12.31) µmol/L, (23.25 ± 11.64) µmol/L], ADMA [(0.21 ± 0.12) µmol/L, (0.23 ± 0.13) µmol/L, (0.21 ± 0.09) µmol/L] and serum NO [(64.14 ± 15.07) µmol/L, (65.29 ± 15.04) µmol/L, (65.32 ± 13.58) µmol/L], eNOS [(20.02 ± 4.50) µg/L, (20.79 ± 4.03) µg/L, (19.82 ± 5.70) µg/L] remained unchanged during the 12 weeks therapy (all P > 0.05). In group 2, concentrations of plasma Hcy [(12.54 ± 6.49) µmol/L] and ADMA[(0.18 ± 0.07) µmol/L] were significantly decreased after the treatment of 12 weeks than the treatment baseline value [(21.51 ± 7.82) µmol/L, (0.20 ± 0.12) µmol/L] and 2 weeks value[(19.38 ± 8.14) µmol/L, (0.21 ± 0.12) µmol/L], however the concentrations of serum NO and eNOS showed contrary results of the Hcy and ADMA's. (all P < 0.05). In group 3, similar changes occurred at 2 weeks after therapy (P < 0.05 2 weeks vs. baseline and 12 weeks vs. 2 weeks). Plasma ADMA level was positively correlated with Hcy at baseline (r = 0.546, P < 0.05). CONCLUSIONS Supplementation of folic acid, VitB(12) and/or probucol helps to improve endothelial function and reduce plasma Hcy and ADMA levels in patients with hypertension.