Genetic Variations of Oxidative Stress Related Genes ALOX5, ALOX5AP and MPO Modulate Ischemic Stroke Susceptibility Through Main Effects and Epistatic Interactions in a Chinese Population

Cell Physiol Biochem. 2017;43(4):1588-1602. doi: 10.1159/000482023. Epub 2017 Oct 17.

Abstract

Background/aims: To investigate the roles of the oxidative stress related-genes ALOX5, ALOX5AP and MPO in ischemic stroke susceptibility in the Han Chinese population.

Methods: A total of 351 ischemic stroke patients and 417 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 gene polymorphisms were genotyped.

Results: We identified that rs2107545 of MPO gene was significantly associated with ischemic stroke susceptibility after adjusting for covariates. Furthermore, we also considered the likely complexity of oxidative stress and inflammatory process in stroke by assessing the combined effects of multiple genes. Generalized multifactor dimensionality reduction (GMDR) analysis revealed that the combination of ALOX5 rs10900213, ALOX5AP rs4293222 and MPO rs2107545 was significantly associated with increased risk of ischemic stroke (P=0.0040, OR (95% CI) =1.991 (1.241 to 3.195)). Additionally, the MPO rs2107545 genotype was significantly associated with clinical outcomes at 6 months after discharge from the hospital.

Conclusion: Our study revealed that epistatic interaction among the ALOX5, ALOX5AP and MPO genes played a significant role in vulnerability to ischemic stroke. Furthermore, these results also suggest that the rs2107545 of MPO gene can be used as a biomarker for the susceptibility and prognosis of ischemic stroke patients.

Keywords: ALOX5 gene; ALOX5AP gene; Epistatic interactions; Genetic main effects; Ischemic stroke prognosis; Ischemic stroke susceptibility; MPO gene; Oxidative stress.

MeSH terms

  • 5-Lipoxygenase-Activating Proteins / genetics*
  • Aged
  • Arachidonate 5-Lipoxygenase / genetics*
  • Asian People / genetics
  • Brain Ischemia / epidemiology
  • Brain Ischemia / genetics*
  • Case-Control Studies
  • China / epidemiology
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress
  • Peroxidase / genetics*
  • Polymorphism, Single Nucleotide*
  • Stroke / epidemiology
  • Stroke / genetics*

Substances

  • 5-Lipoxygenase-Activating Proteins
  • ALOX5AP protein, human
  • Peroxidase
  • Arachidonate 5-Lipoxygenase
  • ALOX5 protein, human