AGT rs4762 is associated with diastolic blood pressure in Mexicans with diabetic nephropathy

• Published in: Journal of diabetes and its complications 2021-03, Vol.35 (3), p.107826, Article 107826
• Main Authors: Vázquez-Moreno, Miguel, Locia-Morales, Daniel, Peralta-Romero, José, Sharma, Tanmay, Meyre, David, Cruz, Miguel, Flores-Alfaro, Eugenia, Valladares-Salgado, Adan
• Format: Article
• Language: English
• Subjects: Adipocytes; Adult; Albumins; Angiotensinogen - genetics; Angiotensinogen gene; Blood Pressure; Cholesterol; Creatinine; Deoxyribonucleic acid; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetic Nephropathies - diagnosis; Diabetic Nephropathies - genetics; Diabetic nephropathy; Diastolic blood pressure; DNA; Genomes; Humans; Hyperglycemia; Hypertension; Kidney diseases; Mexican population; Mexico; Pathogenesis; Population; Regression analysis; Regulation; Renin-Angiotensin System - genetics
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2020.107826

Since angiotensinogen has a pivotal role in the renin-angiotensin-aldosterone system, the analysis of polymorphisms of the angiotensinogen (AGT) gene could help explain its potential involvement in hypertension and diabetic nephropathy (DN) pathogenesis. For that reason, we investigated 1) the association of AGT rs4762 with blood pressure (BP) and kidney function-related traits and 2) the interaction effect of AGT rs4762 with DN on BP and kidney function-related traits in 546 Mexican adults with type 2 diabetes (T2D). We enrolled 546 unrelated Mexican patients with T2D (350 cases with DN and 196 controls without DN). AGT rs4762 was genotyped in all participants using TaqMan technology (effect allele: A). BP and kidney function-related traits, including serum urea and creatinine, urinary albumin, urine albumin to urine creatinine ratio (ACR), and glomerular filtration rate, were studied. DN was defined as having a previous diagnosis of T2D and an ACR ≥ 30 mg/g. The association between these parameters was investigated using logistic regression with adjustment for covariates. AGT rs4762 A allele was significantly associated with diastolic blood pressure (N = 546, β = 1.243 ± 0.918, p = 0.029). A significant interaction between DN and AGT rs4762 was also observed in relation to diastolic blood pressure (DBP) (N = 546, β = 0.930 ± 0.433, p=0.032). A follow-up analysis of simple effects particularly revealed a positive association between AGT rs4762 A allele and DBP only in patients with diabetic nephropathy (N = 350, β = 2.837 ± 1.267, p = 0.026). Our results evidence that, although AGT rs4762 is not associated with DN, the AGT rs4762 A allele is positively associated with DBP in the Mexican population with DN. •Contemporary disease pathogenesis models link diabetic nephropathy to genetic factors associated with the regulation of blood pressure.•A significant interaction between diabetic nephropathy and AGT rs4762 is observed in relation to diastolic blood pressure.•AGT rs4762 A allele is significantly associated with diastolic blood pressure only in patients with diabetic nephropathy.