Single Nucleotide Polymorphism (C677T) in the MTHFR Gene and Essential Hypertension: A Pilot Study

Abstract

Hypertension constitutes a global public health problem as it affects almost one third of adults worldwide, and is estimated to cause 9.4 million deaths every year, and about 13% of the total annual deaths. It affects about 26.3% of the adult Egyptian population. Hypertension is a major risk factor for coronary heart disease and cerebro-vascular disease. Progression of hypertension has been shown to be strongly associated with cardiac and vascular abnormalities that cause damage of the heart, kidneys, brain, retina, and other organs as well. It is reported as being responsible for at least 45% of deaths due to cardiac diseases and 51% of those due to stroke, which made the world health organization (WHO) to report hypertension as the first cause of death worldwide. Essential hypertension accounts for 95% of all cases of hypertension. The development of EH is influenced by genetic, environmental, demographic factors and their interactions. Many genes and polymorphisms have been presumed to be involved in the pathogenesis of EH. Among those genes is the C677T polymorphisms in methylene-tetrahydrofolate reductase (MTHFR) gene. Methylene tetrahydrofolate reductase enzyme is involved in folate and homocysteine metabolism and whose mutation causes increased homocysteine levels that cause damage to the vascular and nervous systems. We conducted this study to assess the association between C667T MTHFR gene polymorphism and EH among adult Egyptian; it included 100 subjects in two groups. The cases group included 70 subjects, diagnosed with EH and the control group included 30 apparently healthy subjects with normal BP. Real time PCR was done to detect C667T MTHFR gene polymorphism using whole blood EDTA samples. Our results revealed highly significant frequency of DM, cardiac disease and family history of HTN among cases compared to control group. Regarding the C667T polymorphism, a higher frequency was detected among cases (60%) than controls (26.7%) with a highly significant difference between them (p =0.002). Genotypic analysis of the cases regarding C667T MTHFR revealed that 28 patients (40%) had wild genotype (CC) type, While 42 patients (60%) had mutant type, 37 of them (52.9%) were heterozygous genotype (CT) and 5 (7.1%) were homozygous genotype (TT). Comparing both genotype of MTHFR gene mutation (wild type and mutant type both heterozygous and homozygous) as regards association with risk factors as DM, cardiac disease, kidney disease and family history of HTN revealed no statistical significance with any of these parameters.