Association of gene polymorphism methylenetetrahydrofolate reductase cytosine-to-thymidine substitution at nucleotide 677 with cardiovascular and metabolic risk in morbidly obese patients

Rea Levicki; Juraj Jug; Ines Vinković; Filip Mustač; Martina Matovinović; Lada Bradić; Jadranka Sertić; Martina Lovrić Benčić

doi:10.15836/ccar2019.235

Authors

Rea Levicki — Požega General County Hospital, Požega, Croatia — ORCID: 0000-0003-3687-1310
Juraj Jug — University of Zagreb School of Medicine, Zagreb, Croatia — ORCID: 0000-0002-3189-1518
Ines Vinković — University of Zagreb School of Medicine, Zagreb, Croatia — ORCID: 0000-0003-1705-8295
Filip Mustač — University of Zagreb School of Medicine, Zagreb, Croatia — ORCID: 0000-0003-2851-6183
Martina Matovinović — University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0002-6325-7394
Lada Bradić — University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0001-8296-699X
Jadranka Sertić — University Hospital Centre Zagreb, Zagreb, Croatia
Martina Lovrić Benčić — University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0001-8446-6120

Abstract

**Introduction**: Region near the gene encoding methylenetetrahydrofolate reductase (MTHFR) is among eight loci associated with blood pressure. (1-3) The aim of this study is to show connection between polymorphism of MTHFR C667T and hypertension, diabetes, prediabetes and obstructive sleep apnea in obese Croatian patients. **Patients and Methods**: We included 88 patients from a multidisciplinary weight management program in which genetic analysis on MTHFR gene polymorphism was tested. Patients were divided in 3 groups: 36 patients with MTHFR C677T healthy genotype CC (27 women, 9 men; age 46.4±10.1 year; BMI 44.9±8.8 kg/m2), 38 patients with MTHFR C677T heterozygous mutation CT (27 women, 11 men; age 46.9±11.4 year; BMI 44.6±8.6 kg/m2), 14 patients with MTHFR C677T homozygous mutation TT (12 women, 2 men; age 50.1±15.5 year; BMI 40.2±6.9 kg/m2). In each group the incidence of hypertension, prediabetes, diabetes and obstructive sleep apnea (OSA) was determined. **Results**: Patients with genetic mutation MTHFR C677T:CT (**Figure 1**) had the highest incidence of arterial hypertension (65.8%), diabetes (18.4%), prediabetes (18.4%) and OSA (31.6%) with the highest average apnea hypopnea index (AHI) of 17.3±24.7, even 13.2% of patients used continuous positive airway pressure (CPAP). Patients with healthy genotype MTHFR C677T:CC had lower incidence of arterial hypertension (44.4%), prediabetes (11.1%), diabetes (13.9%), OSA (25%), average AHI 11.3±15.9 and only 8% of patients used CPAP. Patients with MTHFR C677T:TT polymorphism had the lowest arterial hypertension incidence (42.9%), the highest prediabetes incidence (42.9%), middle OSA prevalence (28.6%), AHI 7.7±7.6. FIGURE 1. The graph shows hypertension, prediabetes and obstructive sleep apnea distribution in the group of patients with methylenetetrahydrofolate reductase cytosine-to-thymidine substitution at nucleotide 677 healthy genotype CC, heterozygous mutation CT and homozygous mutation TT. MTHFR C677T:CC - methylenetetrahydrofolate reductase cytosine-to-thymidine substitution at nucleotide 677 healthy genotype CC; MTHFR C677T:CT - methylenetetrahydrofolate reductase cytosine-to-thymidine substitution at nucleotide 677 heterozygous mutation CT; MTHFR C677T:TT - methylenetetrahydrofolate reductase cytosine-to-thymidine substitution at nucleotide 677 homozygous mutation TT. **Conclusion**: MTHFR C677T:CT polymorphism is the most common gene polymorphism in our group of morbidly obese patients. MTHFR C677T:CT polymorphism compared to MTHFR C677T:CC and MTHFR C677T:TT polymorphisms carries the highest risk for arterial hypertension, metabolic disorders (diabetes) and obstructive sleep apnea. Homozygotes MTHFR C677T:TT carries the highest risk for prediabetes. Further investigation is needed to explore this correlation.

Keywords

methylenetetrahydrofolate reductase, hypertension, diabetes

DOI

https://doi.org/10.15836/ccar2019.235

Literature

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