CC Cardiol Croat Cardiologia Croatica Cardiol. Croat. 1848-543X 1848-5448 Croatian Cardiac Society CC 2019 14_9-10_235 10.15836/ccar2019.235 Extended Abstract Association of gene polymorphism methylenetetrahydrofolate reductase cytosine-to-thymidine substitution at nucleotide 677 with cardiovascular and metabolic risk in morbidly obese patients https://orcid.org/0000-0003-3687-1310LevickiRea1* https://orcid.org/0000-0002-3189-1518JugJuraj2 https://orcid.org/0000-0003-1705-8295VinkovićInes2 https://orcid.org/0000-0003-2851-6183MustačFilip2 https://orcid.org/0000-0002-6325-7394MatovinovićMartina3 https://orcid.org/0000-0001-8296-699XBradićLada3 SertićJadranka3 https://orcid.org/0000-0001-8446-6120Lovrić BenčićMartina3 Požega General County Hospital, Požega, Croatia University of Zagreb School of Medicine, Zagreb, Croatia University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia ADDRESS FOR CORRESPONDENCE: Rea Levicki, Opća županijska bolnica Požega, A. Starčevića 4, HR-35000 Slavonski Brod, Croatia. / Phone: +385-98-550-309 / E-mail: rlevicki@gmail.com 102019 14 9-10 235 235 05082019 16092019 2019 Croatian Cardiac Society KEYWORDS: methylenetetrahydrofolate reductasehypertensiondiabetes

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.

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.

LITERATURE McNultyHStrainJJHughesCFWardM. Riboflavin, MTHFR genotype and blood pressure: A personalized approach to prevention and treatment of hypertension. Mol Aspects Med. 2017 Feb;53:2–9. 10.1016/j.mam.2016.10.00227720779 WuYLHuCYLuSSGongFFFengFQianZZ Association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and essential hypertension: a systematic review and meta-analysis. Metabolism. 2014 Dec;63(12):1503–11. 10.1016/j.metabol.2014.10.00125458833 YigitSKarakusNInanirA. Association of MTHFR gene C677T mutation with diabetic peripheral neuropathy and diabetic retinopathy. Mol Vis. 2013 Jul 25;19:1626–30.23901246