## 4 Discussion  
This study assessed the role of the Tth111I, ER22/ER23, and N363S-_NR3C1_ gene polymorphisms in the development of CA stenosis in the Polish population with CAD. We have not shown any connection between CA stenosis and the genetic variants, alleles, or haplotypes of _NR3C1_ gene. To the best of our knowledge, our study is the first to investigate the association between Thh111I, ER22/ER23, and N363S-_NR3C1_ gene polymorphisms and the CA stenosis. The strength of our study is determined by the very well documented homogeneous cohort of individuals undergoing angiography balanced with the control group. The limitation of this research is the relatively small study group. Additionally, the control group was younger than the CS group, which may have had some impact on the obtained results. Certainly, another limitation is the lack of determinations of inflammatory factors (including GCs) in the blood serum. Moreover, both CS and CG have already been treated for CAD, which could modulate, or even to some extent, extinguish the inflammatory process in the vessels [24]. Atherosclerosis, stenosis, or contraction of the CA decreases brain perfusion, potentially causing ischemic stroke. Thus, atherosclerosis in the CA is a crucial factor in the pathobiology of brain symptoms and is considered an independent risk factor for cerebral events. A complex interaction between the environmental factors, genetic components, and inflammation leads to the initiation and progression of atherosclerosis [5]. Particular attention should be paid to the inflammatory process. Despite researchers' efforts, its exact mechanism is still not entirely clear. In the large multiethnic study, the links between none of 1348 _ALOX5_ (archidonate 5-lipoxygenase, 5-LOX) polymorphisms and subclinical atherosclerosis, as well as CAD events, were found [25]. Polymorphisms in this gene increase the inflammatory production of leukotrienes. It may contribute to the promotion of inappropriate or excessive vasculitis, leading to atherosclerosis and potential CVD [26; 27; 28]. Another study reported the supposed modifying effect of a diet rich in omega-3 and -6 fatty acids on the relationship between ALOX5 tandem variability and atherosclerosis [29]. However, in the multiethnic study by [PERSON] et al., such a relationship has not been confirmed [25]. In the study on the Netherlands population, [PERSON] et al. found that the ER22/23 EK polymorphism of the GR gene was associated with lower C-reactive protein (CRP) levels and better survival rate in older men. This can be related to subtle lifelong GC resistance [30]. In contrast, a relatively large study of the South-West Germany population with weakly presented standard risk factors investigated the association between 16 pro-inflammatory genes and the incidence of stroke. It has been shown that the more pro-inflammatory genetic profile, the higher risk of stroke. Furthermore, some polymorphisms in the CRP gene, which cause its overexpression, are likely to increase the risk of CAD and myocardial infarction (MI) [31; 32]. However, in our previous study of the Polish population, no connection was discovered between polymorphisms of pro-inflammatory cytokines such as IL1B C(-31)T/IL1 RN (VNTR) or their haplotypes and \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Parameter** & **Thh111I Genotype** & **N363S Genotype** & **ER22/ER23 EK Genotype** \\ \hline BMI (kg/m\({}^{2}\)) & 0.411 & 0.168 & 0.738 \\ \hline Dyslipidemia & 0.475 & 0.325 & 0.584 \\ \hline DM & 0.454 & 0.671 & 0.573 \\ \hline HT & 0.496 & 0.741 & 1.0 \\ \hline \hline \end{tabular} DM—diabetes mellitus; HT—arterial hypertension. Data are given as mean \(p\)-values calculated with the Kruskal-Wallis test for quantitative variables and with the \(\chi^{2}\) test for qualitative variables.  
\end{table} 
Table 7: Associations of Thh111I, N363S, and ER22/23 EK variants of NR3C1 gene and metabolic profile. CAD [33; 34].