Association of Genes Related to Oxidative Stress with the Extent of Coronary Atherosclerosis

Abstract

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.

The role and mechanism of tetramethylpyrazine for atherosclerosis in animal models: A systematic review and meta-analysis

“…In the initiation and progression of atherosclerosis, oxidative stress plays a critical role [ 41 ]. Nrf-2 is a transcription factor related to antioxidant stress that increases endogenous antioxidant activity, reducing oxidative stress in the body [ 42 ].…”

Total impact of oxidative stress genes on cardiovascular events—a 7-year follow-up study

“…Health-related data from 1905 patients referred for diagnostic coronary angiography to the First Department of Cardiology of the Medical University of Gdansk between 2003 and 2006 were used to compile a study population (Wirtwein et al 2017;Wirtwein et al 2018). In this project, as in our previous publication (Racis et al 2020b), the same group with coronary atherosclerosis confirmed in coronary angiography was enrolled; however, the final analysis was conducted on 1020 individuals since 79 patients lacked follow-up data; detailed inclusion and exclusion criteria are presented in Fig. 1.…”

“…Selection criteria included the following: (1) SNP has been described as functional in previous studies, and ( 2 S1. The risk alleles were defined according to their potential to increase the extent of atherosclerosis, as presented in our previous publication (Racis et al 2020b). After each SNP was investigated individually, the additive effect of the eight SNPs was analysed as a GRS that reflected the total impact of genetic variants.…”

“…The choice of the pro-atherosclerotic variant in each locus was based on the results of studies referenced in Table 1 and the results of our research (Racis et al 2020b), where those variants were studied in association with the extent of coronary atherosclerosis.…”

Роль Поліморфізму SOD2 У Пацієнтів З Артеріальною Гіпертензією Та Субклінічним Гіпотиреозом

“…Наявність поліморфного варіанта rs4880 SOD2 С47Т, при якому відбувається амінокислотна заміна Ala16Val, змінює структуру ферменту, зменшуючи ефективність його надходження в мітохондріальний матрикс, і, отже, зменшує вироблення H 2 O 2 . Проте наявні дані ролі поліморфізму rs4880 SOD2 у формуванні ризику розвитку серцево-судинних захворювань суперечливі: деякі автори стверджують, що алель ризику С, інші -що генотип ТТ збільшує ризик, проте є й дослідження, у яких не було виявлено жодних асоціацій [13][14][15]. Доступна інформація стосовно впливу поліморфізму SOD2 на формування патологічних змін при АГ досить обмежена, а при СГ і навіть маніфестному гіпотиреозі взагалі відсутня, хоча є багато даних щодо ролі rs4880 SOD2 на розвиток та перебіг злоякісних новоутворень щитоподібної залози [16].…”