Associations of MTRR A66G polymorphism and promoter methylation with ischemic stroke in patients with hyperhomocysteinemia

J Gene Med. 2020 May;22(5):e3170. doi: 10.1002/jgm.3170. Epub 2020 Feb 17.

Abstract

Background: Patients with hyperhomocysteinemia (HHcy) have a higher risk of developing ischemic stroke (IS). The association between MTRR A66G polymorphism and promoter methylation with IS in patients with HHcy is also uncertain. The present study aimed to investigate the association between the MTRR polymorphism and methylation with IS in HHcy patients.

Methods: This case-control study included a total of 304 HHcy patients (95 with IS and 209 without IS). Multivariate logistic regression analyses were applied to explore the association between MTRR polymorphism and classical atherothrombotic risk factors with the risk of IS.

Results: The log-additive and dominant models were markedly different in participants with IS compared to the control group (p = 0.031 and 0.016, respectively). The log-additive and dominant showed a significant association with IS in the low level plasma homocysteine groups (p = 0.024 and 0.014, respectively). No significant difference of methylation between IS and without IS group (p > 0.05). Patients with high plasma homocysteine had a 4.041-4.941 fold higher risk of IS (p = 0.01, 0.016 and 0.041, respectively) compared to the low plasma homocysteine group. Age, diabetes, hypertension and plasma homocysteine were the risk factors for IS in patients with HHcy (p = 0.033, 0.000, 0.001 and 0.038, respectively).

Conclusions: MTRR A66G polymorphism and an elevated plasma plasma homocysteine level were significantly associated with an increased risk of IS in patients with HHcy. Age, diabetes, hypertension and Hcy were all found to be associated with IS.

Keywords: MTRR; hyperhomocysteinemia; ischemic stroke; methylation; polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • DNA Methylation
  • Female
  • Ferredoxin-NADP Reductase / genetics*
  • Genetic Predisposition to Disease*
  • Homocysteine / blood*
  • Humans
  • Hyperhomocysteinemia / blood*
  • Hyperhomocysteinemia / complications
  • Hyperhomocysteinemia / genetics*
  • Hyperhomocysteinemia / physiopathology
  • Ischemic Stroke / blood*
  • Ischemic Stroke / complications
  • Ischemic Stroke / genetics*
  • Ischemic Stroke / metabolism
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Risk Factors

Substances

  • Homocysteine
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase