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Polymorphism of the methylenetetrahydrofolate reductase gene C677T and its influence on the antihypertensive and vascular protective effects of short-term lercanidipine treatment
Authors:Xu Huifeng  Zheng Huan  Shen Yi  Huang Junling  Luo Ming
Affiliation:Tongji Hospital, No. 389 Xincun Road, Shanghai, China.
Abstract:

Objective

To determine whether the antihypertensive and vascular protective effects of short-term treatment with lercanidipine, a calcium channel blocker, are modulated by the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism.

Methods

In a self-controlled study, a total of 143 essential hypertensive patients, all permanent residents of Shanghai, were included. All of them were treated orally with lercanidipine at a single daily fixed dosage of 10 mg for 28 consecutive days and the genotypes of the MTHFR C677T polymorphism were determined. Blood pressures, ankle-brachial index values (ABI), and pulse wave velocity (PWV) were measured at baseline and on the 29th day.

Results

The 110 subjects for whom complete genotype and phenotype information were available were used for final data analysis. Patients with the TT genotype showed higher baseline diastolic blood pressure (DBP) than those with the CC and CT genotypes (P = 0.018). Within each genotype group, SBP, DBP and PWV showed significant difference between baseline and after treatment (P < 0.05). However, ABI showed significant difference between baseline and after treatment only within the CT and TT groups (P < 0.05) but not in the CC group (P > 0.05). Patients with the TT genotype presented a greater reduction in normalized PWV than those with the CC and CT genotypes (P = 0.02). Patients in all genotype groups had statistically similar changes in normalized SBP, DBP and ABI (P > 0.05).

Conclusion

The MTHFR gene polymorphism C677T might be associated with the vascular protective effects of short-term lercanidipine treatment. However, the MTHFR C677T polymorphism might not affect the antihypertensive effects of the lercanidipine treatment.
Keywords:MTHFR, methylenetetrahydrofolate reductase   ABI, ankle-brachial index values   PWV, pulse wave velocity   SBP, systolic blood pressure   DBP, diastolic blood pressure   Hcy, homocysteine   ROS, reactive oxygen species   CCBs, calcium channel blockers   VGCCs, voltage-gated calcium channels   WHO, World Health Organization   ΔBP, blood pressure response   PAD, peripheral arterial disease   AHA, American Heart Association   BMI, body mass index   VSMC, vascular smooth muscle cell   ECM, extracellular matrix
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