The association of MTHFR (rs1801133) with hypertension in an indigenous south African population

Sihle E Mabhida; Jyoti R Sharma; Teke Apalata; Charity Masilela; Sibusiso Nomatshila; Lawrence Mabasa; Hannah Fokkens; Mongi Benjeddou; Babu Muhamed; Samukelisiwe Shabalala; Rabia Johnson

doi:10.3389/fgene.2022.937639

The association of MTHFR (rs1801133) with hypertension in an indigenous south African population

Front Genet. 2022 Jul 22:13:937639. doi: 10.3389/fgene.2022.937639. eCollection 2022.

Authors

Sihle E Mabhida^{1

2}, Jyoti R Sharma¹, Teke Apalata³, Charity Masilela⁴, Sibusiso Nomatshila⁵, Lawrence Mabasa¹, Hannah Fokkens^{1

6}, Mongi Benjeddou², Babu Muhamed⁷, Samukelisiwe Shabalala¹, Rabia Johnson^{1

6}

Affiliations

¹ Biomedical Research and Innovation Platform, SAMRC, Tygerberg, South Africa.
² Department of Biotechnology, Faculty of Natural Science, University of the Western Cape, Cape Town, South Africa.
³ Division of Medical Microbiology, Department of Laboratory-Medicine and Pathology, Faculty of Health Sciences, Walter Sisulu University and National Health Laboratory Services, Mthatha, South Africa.
⁴ Department of Biochemistry, North-West University, Mmabatho, South Africa.
⁵ Division of Preventive Medicine and Health Behavior, Department of Public Health, Faculty of Health Sciences, Walter Sisulu University, Mthatha, South Africa.
⁶ Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
⁷ Division of Infections Disease - University of Tennessee Health Sciences Center (UTHSC), Memphis, TN, United States.

Abstract

Aims: The current study sought to investigate the association between the methylenetetrahydrofolate reductase (MTHFR) variant (rs1801133) and the risk of developing hypertension (HTN) in an indigenous South African population. Methods: A total of 442 participants (hypertensive, n = 279 and non-hypertensive, n = 163) from the indigenous tribe residing in Mthatha, Eastern Cape (South Africa) were recruited. HTN was defined as a systolic (SBP) and diastolic blood pressure (DBP) of ≥130/80 mmHg following American Heart Association guidelines. The genotyping of MTHFR (rs1801133) was assessed using MassARRAY^® System. Thereafter, the association between rs1801133 in various genetic models and HTN was determined by logistic regression model analysis. Furthermore, the interaction between rs1801133 and selected risk factors on HTN was performed using the open-source multifactor dimensionality reduction (MDR). Results: The low frequency of the T allele (5%) was also observed when compared with the C allele (95%) in both cases and controls. After adjusting for confounding factors (gender, smoking status, BMI, and blood glucose levels), there were no significant associations were observed between rs1801133 and the risk of HTN in all genetic models: genotypic (OR 0.75, 95% CI 0.29-1.95, p = 0.56), dominant (OR 0.86, 95% CI 0.35-2.16, p = 0.75), co-dominant (OR 1.33, 95% CI 0.51-3.48, p = 0.55) and allelic (OR 0.80, 95% CI 0.49-1.62, p = 0.70) in logistic regression analysis. However, a significant interaction was reported among rs1801133, age, and gender (p < 0.0001) with the risk of HTN. Conclusion: The present study reports on the lack of association between MTHFR (rs1801133) and the risk of HTN in an indigenous South African tribe. However, an interaction between gender, age, and rs1801133 was observed. Thus, future studies with a large sample size are required to further validate these findings.

Keywords: Africa; MTHFR; genetic variation; hypertension; methylenetetrahydrofolate reductase gene; single-nucleotide polymorphism.