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. 2023 May 23;9(6):e16444.
doi: 10.1016/j.heliyon.2023.e16444. eCollection 2023 Jun.

Homocysteine levels, H-Hypertension, and the MTHFR C677T genotypes: A complex interaction

Cynthia Al Hageh  1 , Eman Alefishat  1   2   3 , Michella Ghassibe-Sabbagh  4 , Daniel E Platt  5 , Hamdan Hamdan  1 , Raya Tcheroyan  6 , Elie Chammas  7 , Siobhán O'Sullivan  1 , Antoine Abchee  8 , Binyan Wang  9 , Xiping Xu  10 , Moni Nader  1   3 , Pierre Zalloua  1   3   11
Affiliations

Homocysteine levels, H-Hypertension, and the MTHFR C677T genotypes: A complex interaction

Cynthia Al Hageh et al. Heliyon. .

Abstract

Background and objectives: High homocysteine levels are associated with increased risk of hypertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase (MTHFR). We aimed to investigate the levels of homocysteine and their association with hypertension, stroke, and antihypertensive medication usage in patients with different MTHFR C677T genotypes.

Methods and results: Genotype frequency of MTHFR polymorphism was performed, and plasma homocysteine levels were measured in 2,640 adult Lebanese patients. Hypertension, history of stroke, and list of medications were documented, among other clinical and demographic parameters. The TT mutant genotype and the T mutant allele of MTHFR were more prevalent in hyperhomocysteinemia (HHcy) and H-hypertensive (H-HTN, defined as hypertension with hyperhomocysteinemia) patients when compared to non-HHcy subjects and non H-HTN patients respectively. Homocysteine levels were significantly higher in hypertensive patients specifically among those on diuretics. A higher level of homocysteine was found in hypertensive patients with the MTHFR T allele compared to patients carrying the C allele. Among the T allele carriers, the average plasma homocysteine level was 13.3 ± 0.193 μmol/L for hypertensive subjects compared to 11.9 ± 0.173 μmol/L (non-hypertensives). Furthermore, homocysteine levels significantly correlated with stroke risk in patients with the T alleles.

Conclusions: We found an association of homocysteine with hypertension, hypertensive medication, and stroke risk among patients with the MTHFR T allele and the TT genotype. The association of diuretics therapy with higher homocysteine levels calls for routine measurements and therapeutic control of homocysteine in patients on diuretic, to improve health-related outcomes.

Keywords: C677T; Diuretics; H-hypertension; HHcy; MTHFR; rs1801133.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Genotypes and allele frequencies (in %) of MTHFR C677T according to hyperhomocysteinemia (HHcy) groups.
Fig. 2
Fig. 2
Homocysteine levels and MTHFR alleles according to (a) hypertension status, (b) diuretics intake and (c) stroke.
See this image and copyright information in PMC

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