Institute of Biomedicine, Anhui Medical University, Hefei, P.R. China.
Pharmacogenet Genomics. 2012 Jun;22(6):421-8. doi: 10.1097/FPC.0b013e32834ac5e8.
To assess the influence of individual methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase A2756G polymorphisms on the change of serum folate concentration in response to different dosages and durations of folic acid (FA) supplementation in hypertensive Chinese adults.
A total of 480 patients with mild or moderate essential hypertension were randomly assigned to three treatment groups: (a) enalapril only (10 mg, control group); (b) enalapril FA tablet [10 : 0.4 mg (10 mg of enalapril combined with 0.4 mg of FA), low-FA group]; (c) enalapril FA tablet (10 : 0.8 mg, high-FA group), once daily for 8 weeks. Individual serum folate levels were measured at baseline, and at 4 and 8 weeks posttreatment.
After 4 or 8 weeks of treatment, increases in serum folate were seen across all genotypes and FA dosage groups. However, compared with patients with 677CC genotype, those with CT or TT genotype in the low-FA group and TT genotype in the high-FA group still had significantly lower folate concentrations, particularly women. In the low-FA group, patients with CT or TT genotype showed an attenuated response compared with those with CC genotype (median ratio of folate at week 8 to that at baseline: CC,1.953 vs. CT,1.755 or TT,1.637, P<0.01 for both). Such an attenuated response was not observed in the high-FA group. Yet, only in the high-FA group did serum folate appear to reach a plateau after 4 weeks of treatment in all three MTHFR 677 genotypes and the methionine synthase 2756 AG/GG genotype.
We demonstrated that MTHFR C677T polymorphisms can not only affect serum folate levels at the baseline and post-FA treatment, but also therapeutic responses to various dosages and durations of FA supplementation.
评估个体亚甲基四氢叶酸还原酶（MTHFR）C677T 和蛋氨酸合成酶 A2756G 多态性对高血压中国成年人接受不同剂量和持续时间叶酸（FA）补充后血清叶酸浓度变化的影响。
共有 480 例轻度或中度原发性高血压患者被随机分配至三组治疗：（a）依那普利单药（10 mg，对照组）；（b）依那普利 FA 片[10：0.4 mg（10 mg 依那普利联合 0.4 mg FA），低 FA 组]；（c）依那普利 FA 片（10：0.8 mg，高 FA 组），每日 1 次，持续 8 周。治疗前、治疗后 4 周和 8 周时分别测量个体血清叶酸水平。
治疗 4 周或 8 周后，所有基因型和 FA 剂量组的血清叶酸水平均增加。然而，与 677CC 基因型患者相比，低 FA 组 CT 或 TT 基因型和高 FA 组 TT 基因型患者的叶酸浓度仍显著较低，尤其是女性。在低 FA 组，与 CC 基因型患者相比，CT 或 TT 基因型患者的反应减弱（第 8 周与基线相比的叶酸中位数比值：CC 为 1.953，CT 为 1.755 或 TT 为 1.637，两者均 P<0.01）。在高 FA 组则未观察到这种反应减弱。然而，仅在高 FA 组中，在所有 3 种 MTHFR 677 基因型和蛋氨酸合成酶 2756 AG/GG 基因型中，在治疗 4 周后，血清叶酸似乎已达到平台期。
我们证明 MTHFR C677T 多态性不仅可以影响基线和 FA 治疗后的血清叶酸水平，还可以影响对不同剂量和持续时间 FA 补充的治疗反应。
