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SELL and GUCY1A1 Gene Polymorphisms in Patients with Unstable Angina
Damian Malinowski1, Magda Zawadzka2, Krzysztof Safranow3
1Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, 70-111 Szczecin, Poland.
Insights
Genetic variations in SELL and GUCY1A1 genes were studied for their link to unstable angina. Certain polymorphisms may influence risk in specific age groups within the Polish population.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Thrombosis Research
Background:
- Acute coronary syndromes, like unstable angina, often stem from atherosclerotic plaque rupture and subsequent thrombus formation.
- Genetic factors, including polymorphisms in genes regulating inflammation and vascular function, can influence the risk of developing coronary artery disease.
- L-selectin (SELL) and Guanylate cyclase 1 soluble subunit alpha 1 (GUCY1A1) are implicated in leukocyte adhesion, inflammation, vasoreactivity, and platelet function, all relevant to thrombotic processes.
Purpose of the Study:
- To investigate the association between specific polymorphisms in the SELL (rs2205849, rs2229569) and GUCY1A1 (rs7692387) genes and the risk of unstable angina pectoris.
- To explore the relationship between these genetic polymorphisms and clinical parameters associated with ischemic heart disease risk.
- To evaluate these associations within the Polish population.
Main Methods:
- Genotyping of SELL rs2205849, rs2229569, and GUCY1A1 rs7692387 polymorphisms in 232 patients diagnosed with unstable angina.
- Coronary angiography was used to confirm significant coronary artery stenosis (>70%) in patients.
- Statistical analysis comparing genotype frequencies between patients and controls, with subgroup analysis based on age (55 years).
Main Results:
- No significant differences in the overall distribution of GUCY1A1 rs7692387, SELL rs2205849, and SELL rs2229569 polymorphisms were observed between the unstable angina group and the control group.
- In patients over 55 years, a decreased frequency of the GUCY1A1 rs7692387AA genotype and increased frequencies of SELL rs2205849 CC and SELL rs2229569 AA genotypes were noted in unstable angina patients.
- Conversely, the GUCY1A1 rs7692387 polymorphism showed a potential increased risk in patients younger than 55 years.
Conclusions:
- The studied SELL and GUCY1A1 polymorphisms are not general risk factors for unstable angina in the Polish population.
- The GUCY1A1 rs7692387 polymorphism may be associated with an increased risk of unstable angina in individuals younger than 55.
- SELL polymorphisms rs2205849 and rs2229569 might be linked to an increased risk of unstable angina in individuals older than 55 in the Polish population.
Abstract:
Acute ischaemia is mostly caused by the rupture of an unstable atherosclerotic plaque in a coronary artery, resulting in platelet accumulation and thrombus formation, which closes the lumen of the coronary vessel. Many different factors can cause atherosclerotic plaques to occlude the lumen of a coronary artery, including factors that increase vascular inflammation and blood platelet aggregation, as well as genetic factors. L-selectin is an adhesion molecule encoded by the human SELL gene, playing an important role in leukocyte adhesion to the endothelium and the development of inflammation. Guanylate cyclase 1 soluble subunit alpha 1 (GUCY1A1) is a gene that affects vasoreactivity and platelet function, thereby influencing thrombotic processes and the risk of developing thrombotic lesions in the coronary vessels. In SELL and GUCY1A1 genes, several polymorphisms have been detected, which may affect gene expression. The aim of our study was to assess the association between the SELL rs2205849 and rs2229569 and GUCY1A1 rs7692387 polymorphisms with the risk of acute coronary syndromes in the form of unstable angina pectoris, and the association between these polymorphisms and selected clinical parameters affecting the risk of developing ischemic heart disease. The study included 232 patients with unstable angina. The diagnosis of unstable angina was achieved by a typical clinical presentation and confirmation of significant coronary artery lumen stenosis (>70%) during coronary angiography. There were no statistically significant differences in GUCY1A1 rs7692387 and SELL rs2205849 and rs2229569 polymorphism distribution between the total study and the control groups. However, when only analysing patients over 55 years of age, we found a decreased frequency of the GUCY1A1 rs7692387AA genotype (AA vs. GA + GG, OR: 0.07; 95% CI: 0.01−0.78) and an increased frequency of the SELL rs2205849 CC genotype (CC vs. TC + TT p = 0.022) and SELL rs2229569 AA genotype (AA vs. GA + GG p = 0.022) in patients with unstable angina. Our results suggest that the SELL rs2205849 and rs2229569 and GUCY1A1 rs7692387 polymorphisms are not risk factors for unstable angina in the Polish population. The GUCY1A1 rs7692387 polymorphism may increase the risk of unstable angina in patients younger than 55 years, while the SELL polymorphisms rs2205849 and rs2229569 may increase the risk of unstable angina in patients older than 55 years in the Polish population.
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