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CYP3A4 and CYP11A1 variants are risk factors for ischemic stroke: a case control study

Ning Gao1, Hong Tang1, Ling Gao1

  • 1Department of Neurosurgery, Affiliated Haikou Hospital of Xiangya Medical College of Central South University, Haikou People's Hospital, #43, People's Avenue, Haidian Island, Haikou, 570208, Hainan, China.

BMC Neurology
|March 5, 2020
PubMed

Insights

Genetic variants in CYP3A4 and CYP11A1 influence ischemic stroke (IS) risk in the Han Chinese population. Certain CYP3A4 and CYP11A1 polymorphisms may offer protection against IS, while others increase susceptibility.

Area of Science:

  • Genetics
  • Cardiovascular Science
  • Pharmacogenomics

Background:

  • Ischemic stroke (IS) poses a significant health burden.
  • Understanding genetic predispositions is crucial for risk stratification.
  • Cytochrome P450 enzymes, including CYP3A4 and CYP11A1, play roles in various physiological processes.

Purpose of the Study:

  • To investigate the association between specific single-nucleotide polymorphisms (SNPs) in CYP3A4 and CYP11A1 genes and the susceptibility to ischemic stroke.
  • To explore potential sex- and age-specific effects of these genetic variants on IS risk.

Main Methods:

  • A case-control study involving 477 IS patients and 493 healthy controls from the Han Chinese population.
  • Genotyping of seven selected SNPs in CYP3A4 and CYP11A1 using Agena MassARRAY.
  • Statistical analysis using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusted for age and gender.

Main Results:

  • CYP3A4 variants rs3735451 and rs4646440 were associated with a decreased risk of IS.
  • CYP3A4 rs4646440 and CYP11A1 rs12912592 showed associations with IS risk in males.
  • Protective effects of CYP3A4 rs3735451 and rs4646440 were observed in individuals over 61 years old.
  • Specific variants in CYP3A4 and CYP11A1 were linked to IS risk in individuals aged 61 years or younger.
  • CYP11A1 rs28681535 genotype correlated with higher high-density lipoprotein cholesterol levels.

Conclusions:

  • Specific polymorphisms in CYP3A4 (rs3735451, rs4646440, rs4646437) and CYP11A1 (rs28681535) may act as protective factors against ischemic stroke in the Han Chinese population.
  • The CYP11A1 rs12912592 polymorphism was identified as a potential risk factor for IS in this population.
  • These findings highlight the potential role of pharmacogenomic variations in IS susceptibility.
Abstract

Keywords:
CYP11A1CYP3A4Ischemic strokePolymorphismSusceptibility

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