Contribution of <i>AGTR</i> 1 Promoter Region Polymorphism to the Progression and Outcome of Sepsis in Patients with Various Comorbidities

Abstract

Blood pressure dysregulation and circulatory failure are major contributors to the progression of sepsis and especially septic shock. One of the genes affecting the vascular endothelium and arteriolar tone is the angiotensin II receptor 1 gene (AGTR1). The AGTR1 rs275651 single-nucleotide polymorphism is associated with the development of angina, high altitude pulmonary edema, and hypertension. The significance of the AGTR1 rs275651 polymorphism in sepsis, particularly in patients with significant comorbidity, has not been studied previously.The aim of the study was to determine the impact of AGTR1 functional polymorphism on sepsis outcome in patients with various comorbidities, including cardiovascular disease and type 2 diabetes mellitus.Material and methods. A prospective study included 144 ICU patients of two clinical hospitals in Moscow, aged 18-75 years with clinical signs of sepsis (Sepsis-3, 2016).Results. In the group of patients with cardiovascular diseases, carriers of the TT AGTR1 rs275651 genotype had a lower mortality rate compared with carriers of the A allele (25 deaths out of 33 versus 16 out of 16, respectively, P=0.041, Fisher's exact test; P=0.0019, log-rank test). In the group of patients with diabetes mellitus (n=62), we also found significant differences in sepsis outcome based on the AGTR1 rs275651 genotype variant. The subgroup of TT AGTR1 rs275651 genotype carriers demonstrated significantly lower mortality compared with TA, AA genotypes carriers (27 deaths out of 41 and 20 out of 21, respectively, P=0.012, Fisher's exact test; OR=10.37; 95% CI: 1.26 to 85.5; P<0.0001, log-rank test).Conclusion. We found an association of the functional polymorphism AGTR1 -777 T>A (rs275651) with sepsis outcome in ICU patients with high-value baseline comorbidity: carriers of the more common TT genotype had lower mortality compared to carriers of the minor A allele.

Keywords

• sepsis
• septic shock
• genetic polymorphism
• agtr1
• angiotensin ii receptor gene
• diabetes mellitus
• comorbidity