BACKGROUND: Type 2 diabetes and arterial hypertension are frequent comorbidities under which activation the renin-angiotensin-aldosterone system is important pathogenetic link. The functional state of the RAAS is genetically determined. Genetic polymorphisms of the RAAS system associated with the development of both type 2 diabetes and arterial hypertension have been identified and mapped. Associations of polymorphic variants of the RAAS genes with type 2 diabetes and arterial hypertension among the inhabitants of Dagestan have not been studied.
AIM: Studying the association of the most relevant polymorphic variants of the C521T and T704C AGT gene, as well as the A1166C AGTR1 gene with type 2 diabetes and when combining type 2 diabetes with arterial hypertension among Dagestan inhabitants.
METHODS: We examined 16 patients with type 2 diabetes, 59 patients with type 2 diabetes combined with arterial hypertension and 51 patients with arterial hypertension, all residents of Dagestan. The control group included 47 healthy persons of the same age group. SNP polymorphisms were investigated by the method of allele-specific Real-Time PCR. The C521T and T704C polymorphisms of the AGT gene and the A1166C polymorphism of the AGTR1 gene were studied.
RESULTS: In the group of patients with a combination type 2 diabetes with arterial hypertension, the genotype CT of the C521T polymorphism of the AGT gene is less common compared to the control (23% vs. 43%, 2 = 3,868, p = 0,049), OR score 0,4 (0,2-0,9 ). The situation is similar with the TC genotype of the T704C polymorphism of the AGT gene (39% versus 61%, 2 = 4,282, p = 0,039). OR was 0,4 (0,20,8).On the contrary, in the same patients, but the carriers of the homozygous CC genotype of the T704C polymorphism of the AGT gene, OR exceeded one and made 2.5 (1.02-5.9), the frequency of occurrence was 42% vs. 23%, 2 = 3,363, p = 0,05. The frequency of the mutant allele C of the A1166C polymorphism of the AGTR1 gene in patients with arterial hypertension alone was 31% vs. 14%, 2 = 5.496, p = 0,019, OR 2,5 (1,2-5,0). The frequency of the wild allele A in these same patients was 69% versus 84%, 2 = 5,496, p = 0,019, OR 0,4 (0,2-0,8). A similar situation is determined with the AA genotype (52% versus 73%, 2 = 3,609, p = 0,05), OR = 0,4 (0,1-0,9).
CONCLUSIONS: The association of the C521T and T704C polymorphisms, as well as the A1166C candidate genes AGT and AGTR1 with type 2 diabetes and arterial hypertension, is an important component in assessing the susceptibility to the development of these diseases in Dagestan residents.
Renin Angiotensin Aldosterone System, Glucose Homeostasis, and Prevention of Type 2 Diabetes: Mechanistic Insights and Evidence from Major Clinical Trials