Association Between Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Multicenter Case-Control Study in Vietnam

Purpose: Diabetic kidney disease (DKD) is one of the major complications of type 2 diabetes mellitus (T2DM), which is common worldwide. Its pathogenesis involves various mechanisms: Notably, overactivation of the renin-angiotensin-aldosterone system (RAAS) and genetic susceptibility. Although RAAS gene polymorphisms have been widely studied, the results vary across various ethnicities. In this study, we investigated the association between the angiotensin-converting enzyme ( ACE ) I/D polymorphism and DKD in the Vietnamese population with T2DM. Patients and Methods: A case-control study was conducted from November 2022 to November 2024 at the University Medical Center at Ho Chi Minh City and Nhan Dan Gia Dinh Hospital. The case group included patients with T2DM and confirmed DKD, while the control group comprised patients with T2DM without DKD. The participants were matched by age and sex. Clinical, biochemical, and genetic data were collected, including those on ACE I/D polymorphisms. Results: A total of 578 patients were enrolled, with 289 in the case group and 289 in the control group. The participants had a mean age of 63.4 ± 10.8 years, of which 41.3% were male. Compared with the controls, patients with DKD experienced longer T2DM durations and higher rates of hypertension, heart failure, and chronic anemia, higher HbA1c levels, and lipid profiles ( p < 0.05). The ACE I/D polymorphism significantly differed between the groups, with the DD genotype being more frequent in the case group ( p < 0.001). This genotype was associated with an increased DKD risk (odds ratio = 2.26; 95% confidence interval: 1.34– 3.81; p = 0.002). Multivariate analysis identified that duration of T2DM, hypertension, triglyceride levels, LDL-C, and the DD genotype were independent risk factors for DKD in patients with T2DM. Conclusion: Among the Vietnamese Kinh population, a significant association was found between the ACE I/D polymorphism and DKD in patients with T2DM. Plain Language Summary: Type 2 diabetes mellitus (T2DM) is a common disease that affects millions of people around the world. One of its most serious complications is diabetic kidney disease (DKD), which can lead to kidney failure and the need for dialysis. Both lifestyle and genetic factors may contribute to who develops DKD, but the specific genetic causes can differ between ethnic groups. In this study, we wanted to find out whether a variation in the angiotensin-converting enzyme (ACE) gene, called the insertion/deletion (I/D) polymorphism, is linked to DKD in Vietnamese people living with T2DM. The ACE gene is part of the body’s renin-angiotensin-aldosterone system (RAAS), which helps regulate blood pressure and kidney function. We studied 578 Vietnamese patients with T2DM from two major hospitals in Ho Chi Minh City. Half of them had DKD, and half did not. We compared their medical information, blood test results, and ACE gene types. We found that people with the DD genotype of the ACE I/D polymorphism were more likely to have DKD. This genetic type, along with factors such as high blood pressure, elevated LDL-C, high triglyceride levels, and longer T2DM duration, increased the risk of DKD. Our findings show that genetics may play an important role in DKD among Vietnamese people with T2DM. Understanding these genetic factors could help doctors identify high-risk patients earlier and personalize treatment to protect kidney health. Keywords: type 2 diabetes mellitus, diabetic kidney disease, I/D variant of the ACE gene, case-control study