Alpha-Adducin 1 (Add1) Gene, Clinical-Demographic and Metabolic Predictors of Arterial Hypertension and Chronic Kidney Disease in Western Ukraine Population

Introduction. Chronic kidney disease (CKD) is a global public health problem affecting about 10% of the population worldwide. Nowadays, the genetic predisposition to CKD development in patients with arterial hypertension (AH) is studied insufficiently. Therefore, the search for early CKD predictors due to hypertension is on the cutting edge of contemporary medicine. Objectives: to evaluate the risk of essential AH (EAH) and CKD in the population of Western Ukraine (North Bukovina) based on some demographic, clinical, and anthropometric data, gender, and alfa adducin 1 gene (ADD1; rs4961). Materials and methods. 100 patients with EAH and 60 practically healthy (control group) participated in the study. All participants underwent clinical and laboratory examinations. Among the risk factors, a burdened anamnesis of cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), body mass index (BMI) in men (M) and women (W) were studied. CKD was defined by glomerular filtration rate (GFR) according to the CKD-EPI equation, taking into account creatinine (cr) and cystatin-C (cys) blood levels (KDIGO, 2024). ADD1 (rs4961) gene polymorphism genotyping was performed by real-time PCR. The results. The risk of EAH is 4 times higher with CVD burdened (95% CI: 1.15-13.88; p=0.027), 8.5 times higher – in the smokers who are carriers of the GG-genotype of the ADD1 gene (rs4961) (OR=8.67; 95% CI: 1.04–72.32; p=0.02), almost 2.5 times higher – with hypercystatinemia-С (≥1.1 mg/l) in T-allele carriers (rs4961), but the difference is significant only in women – by 4.67 times (95% CI: 1.19–18.33; p=0.033). The GG-genotype of the ADD1 gene (rs4961) increases the CKD risk in EAH men by 2.67 times (95% CI: 1.0–7.34; p=0.047). The EAH risk increases regardless of ADD1 gene polymorphic variants (somewhat stronger in patients with mutated T‑allele) in subjects with obesity – by 3.37 and 12 times (95% CI: 1.23–9.24; p=0.014 and 95% CI: 2.24–64.29; p=0.001), in subjects with increased WC (W >88 cm, M >102 cm) – by 4.14 and 45 times (95% CI: 1.49–11.48; p=0.006 and 95% CI: 7.34–275.8; p<0.001), in subjects with increased BMI (≥25.0 kg/m2) and WHR (>0.85 U) – but only in women – by 5.78–9.90 and 30.33–60.67 times (95% CI: 1.12–56.96; p≤0.029–0.008 and 95% CI: 5.58–659.3; p<0.001), respectively. Conclusions. The risk of EAH in the Western Ukraine population increases with burdened CVD heredity, smoking, hypercystatinemia-С in T-allele carriers of the ADD1 gene (rs4961), BMI, WC, and WHR elevation. The GG-genotype of the ADD1 gene increases the CKD risk in hypertensive men.