Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social, Mexico City, Mexico; Laboratorio de Investigación en Epidemiología Clínica y Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico.
J Diabetes Complications. 2021 Mar;35(3):107826. doi: 10.1016/j.jdiacomp.2020.107826. Epub 2020 Dec 31.
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.
血管紧张素原（AGT）在肾素-血管紧张素-醛固酮系统中起着关键作用，因此分析 AGT 基因的多态性有助于解释其在高血压和糖尿病肾病（DN）发病机制中的潜在作用。基于此，我们研究了 1）AGT rs4762 与血压（BP）和肾功能相关特征的关联，以及 2）AGT rs4762 与 DN 对 546 例墨西哥 2 型糖尿病（T2D）患者 BP 和肾功能相关特征的交互作用。
我们纳入了 546 例无血缘关系的墨西哥 T2D 患者（DN 组 350 例，无 DN 组 196 例）。所有参与者均采用 TaqMan 技术（效应等位基因：A）检测 AGT rs4762 基因型。研究了 BP 和肾功能相关特征，包括血清尿素和肌酐、尿白蛋白、尿白蛋白与尿肌酐比值（ACR）和肾小球滤过率。使用 logistic 回归分析调整协变量后，研究了这些参数之间的关联。
AGT rs4762 A 等位基因与舒张压（N=546，β=1.243±0.918，p=0.029）显著相关。DN 和 AGT rs4762 之间也存在显著的交互作用与舒张压（DBP）有关（N=546，β=0.930±0.433，p=0.032）。一项特别的简单效应分析表明，仅在患有糖尿病肾病的患者中，AGT rs4762 A 等位基因与 DBP 呈正相关（N=350，β=2.837±1.267，p=0.026）。
我们的结果表明，尽管 AGT rs4762 与 DN 无关，但在墨西哥患有 DN 的人群中，AGT rs4762 A 等位基因与 DBP 呈正相关。
