Associations of homocysteine status and homocysteine metabolism enzyme polymorphisms with hypertension and dyslipidemia in a Chinese hypertensive population

ABSTRACT

Background: Hypertension (HTN), dyslipidemia and hyperhomocysteinemia (HHcy) are risk factors for cardiovascular disease (CVD).

Methods: Hypertensive Chinese subjects (n = 228) were enrolled. MTHFR C667T, MTHFR A1298C, MTR A2756G, and MTRR A66G genotypes were determined. Unconditional logistic regression was performed to determine the associations of serum Hcy status and genotypes with HTN and dyslipidemia.

Results: The mean age of hypertensive adults was 65.53 ± 9.94 years, including 88 (38.6%) men and 140 (61.4%) women. Patients with MTHFR 667TT and MTRR GG carriers showed higher serum Hcy levels (P = 0.019 and 0.018, respectively), which is associated with higher serum triacylglycerols (TAG) and total cholesterol (TC) levels (P = 0.014 and 0.044, respectively) and a higher risk for hypertriglyceridemia (OR = 1.889, 95% CI: 1.105–3.229, P = 0.020). Compared with low Hcy and MTRR 66AA, those with high Hcy and 66AA or 66AG+GG showed higher odd\s of hypertriglyceridemia (MTRR 66AA+ high Hcy: OR: 2.692, 95% CI: 1.189–6.096, Pcombined = 0.018; MTRR 66AG/GG+ high Hcy: OR: 3.433, 95% CI: 1.517–7.772, Pcombined = 0.003, respectively). Patients with high Hcy and MTHFR 667CC, as well as those with low Hcy and 667CT+TT, showed lower odds of uncontrolled SBP (MTHFR 667CC+ high Hcy: OR: 0.338, 95% CI: 0.115–0.996, Pcombined = 0.049; MTHFR 667CT/TT+ low Hcy: OR: 0.421, 95% CI: 0.193–0.921, Pcombined = 0.030) compared to patients with low Hcy and MTHFR 667CC.

Conclusions: Serum Hcy status and Hcy metabolism gene polymorphisms (MTHFR C667T and MTRR A66G) may have synergistic effects on the prevalence of HTN and dyslipidemia.

KEYWORDS:

• Homocysteine
• blood pressure
• serum lipids
• single nucleotide polymorphisms
• hypertension

Acknowledgments

The authors’ responsibilities were as follows: Z.S., L.Z., and T.M., developed the study concept and theory; X.Y., T.W., Y.W., Y.C., X. L., J.X., recruited subjects, completed the questionnaires and helped to collect blood samples; X.Y., T.W., and J.G. carried out DNA extraction and PCR-RFLP; X.Y. and T.W. carried out the analyses and prepared the manuscript; K.K. revised and proofread the manuscript; T.M., L.Z., and Z.S., had primary responsibility for final content of the manuscript. All authors read and approved the final manuscript.

Conflict of interest

None of the authors reported a conflict of interest.

Supplementary material

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Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant [number 81373058 and 81370082]; China Special Grant for Prevention and Control of Infection Disease under Grant [number 2017ZX10105011]. Thanks for the support of Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment.