Association of Genes Related to Oxidative Stress with the Extent of Coronary Atherosclerosis.
Milena RacisAnna Stanisławska-SachadynWojciech SobiczewskiMarcin WirtweinMichał KrzemińskiNatalia KrawczyńskaJanusz LimonAndrzej RynkiewiczMarcin GruchałaPublished in: Life (Basel, Switzerland) (2020)
Oxidative stress is believed to play a critical role in atherosclerosis initiation and progression. In line with this, in a group of 1099 subjects, we determined eight single nucleotide polymorphisms (SNPs) related to oxidative stress (PON1 c.575A>G, MPO c.-463G>A, SOD2 c.47T>C, GCLM c.-590C>T, NOS3 c.894G>T, NOS3 c.-786T>C, CYBA c.214C>T, and CYBA c.-932A>G) and assessed the extent of atherosclerosis in coronary arteries based on Gensini score. An increased risk of having a Gensini score in the higher half of the distribution was observed for the PON1 c.575G allele (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.004-1.617, p = 0.046). Next, the genetic risk score (GRS) for the additive effect of the total number of pro-oxidative alleles was assessed. We noted an increase in the risk of having a Gensini score above the median with the maximum number of risk alleles (OR = 2.47, 95% CI: 1.19-5.23, p = 0.014). A univariate Spearman's test revealed significant correlation between the total number of pro-oxidant alleles (GRS) and the Gensini score (ρ = 0.068, p = 0.03). In conclusion, the PON1 c.575A>G variant and the high number of risk alleles (GRS) were independent risk factors for a high Gensini score. We suggest, however, that GRS might occur as a more valuable component in adding a predictive value to the genetic background of atherosclerosis.
Keyphrases
- oxidative stress
- genome wide
- cardiovascular disease
- dna damage
- coronary artery disease
- coronary artery
- ischemia reperfusion injury
- diabetic rats
- induced apoptosis
- nitric oxide synthase
- nitric oxide
- copy number
- signaling pathway
- transcription factor
- atrial fibrillation
- gene expression
- left ventricular
- heat shock
- aortic valve
- drug induced
- ejection fraction