MTHFR Polymorphisms Induce Earlier Onset of Hypertension Which Is Ameliorated by Improved Lifestyle

Background: A combination of genetic and environmental factors contributes to the development of hypertension. Polymorphisms of the gene encoding methylenetetrahydrofolate reductase (MTHFR) have been shown to associate with increased risk of hypertension. However, very few studies concentrated on the age of hypertension onset. This cross-sectional study sought to investigate the interaction between MTHFR polymorphisms and lifestyle factors on age of onset of hypertension in the Chinese Han population.   Methods: Totally 5,760 hypertension patients and 14,753 normotensive controls were enrolled during an annual health examination at a single center. Lifestyle factors and disease history were collected through a questionnaire.  Findings We confirmed the MTHFR TT genotype is a risk factor for hypertension (OR=1.15, 95% CI=1.14-1.27), as are age (OR=1.07, 95% CI=1.07-1.08), BMI (OR=1.05, 95% CI=1.047-1.054), hyperhomocysteinemia (OR=1.015, 95% CI=1.008-1.021), and male gender (OR=1.69, 95% CI=1.54-1.87). The age of onset of hypertension in patients harboring the MTHFR 677CT and TT genotypes was 2.03 and 2.07 years earlier, respectively, than individuals with the CC genotype. Family history, overdrinking, male gender, and high BMI were associated with earlier age of onset of hypertension and the risk was cumulative being3.9, 6.5, and 8.4 years earlier in individuals with 1, 2, and 3 risk factors, respectively. Healthy lifestyle factors delayed the age of onset of hypertension including those individuals carrying the MTHFR genetic risk factor.   Interpretation: The MTHFR C677T and TT polymorphisms predispose to earlier age of onset of hypertension. Favorable lifestyle factors substantially delayed the onset of hypertension including in those individuals carrying the MTHFR genetic risk factor. Genetic predisposition to hypertension responded to favorable lifestyle changes eliminating the myth that genetic risk cannot be prevented. Funding: The State Science and Technology Support Program, the Chinese National Natural Science Fund and the Military Healthcare Programs. Declaration of Interest: We declare no competing interests. Ethical Approval: The study was approved by the Ethical Committee of PLA general hospital, Beijing, China. All participants gave informed consent before participation.