Prevalence of MTHFR C677T polymorphism and its association with serum homocysteine and blood pressure among different ethnic groups: insights from a cohort study of Nepal

BMC Cardiovasc Disord. 2025 Mar 29;25(1):235. doi: 10.1186/s12872-025-04690-z.

Abstract

Background: The risk of hypertension varies based on ethnicity, environmental factors, and genetic predispositions. Studies have reported a higher risk of cardiovascular diseases (CVD) and hypertension among the Newar ethnic groups in Nepal. However, the genetic analysis for Methylenetetrahydrofolate reductase (MTHFR C677T) gene mutations, serum homocysteine, and high-sensitivity C-reactive protein (hs-CRP) levels across different ethnicities remains unexplored.

Methods: Sociodemographic information and baseline data of 489 participants were obtained from the first phase of the Dhulikhel Heart Study. Preserved blood samples were analyzed for MTHFR C677T polymorphism using real-time polymerase chain reaction (TaqMan assay), and serum homocysteine was measured through immunoassay techniques. Descriptive analysis, the Hardy-Weinberg equilibrium test, and multinomial regression were performed.

Results: The prevalence of homozygous mutation (TT) was 19.8% in the Newar group and 12.5% in the Brahmin/Chhetri ethnicity. The highest mean value of homocysteine (19.4 µmol/L) was observed in homozygous participants, followed by the heterozygous mutant group (17.4 µmol/L). A statistically significant association (P = < 0.001) was found between homocysteine levels and blood pressure.

Conclusions: The Dhulikhel Heart Study reveals a significant prevalence of the MTHFR C677T gene mutation among the Newar ethnicity compared to other groups. Elevated levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP) were associated with increased blood pressure.

Clinical trial number: Not applicable.

Keywords: Hyperhomocysteinemia; Hypertension; MTHFR C677T; Nepal; Polymorphism.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • Biomarkers / blood
  • Blood Pressure* / genetics
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homocysteine* / blood
  • Homozygote
  • Humans
  • Hyperhomocysteinemia* / blood
  • Hyperhomocysteinemia* / diagnosis
  • Hyperhomocysteinemia* / ethnology
  • Hyperhomocysteinemia* / genetics
  • Hypertension* / blood
  • Hypertension* / diagnosis
  • Hypertension* / ethnology
  • Hypertension* / genetics
  • Hypertension* / physiopathology
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)* / genetics
  • Middle Aged
  • Nepal / epidemiology
  • Phenotype
  • Prevalence
  • Risk Assessment
  • Risk Factors

Substances

  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Homocysteine
  • MTHFR protein, human
  • C-Reactive Protein
  • Biomarkers