Genetic Based Risk Score Prediction for the Development of Diabetic Nephropathy in Children and Adolescents with Type 1 Diabetes
Project no. 22262 · Status: Kapanmış · 2020
Summary
<p>Introduction: The pathogenesis of diabetic nephropathy (DN) is multifactorial, however most of its development mechanisms are remain unknown. According to DCCT/EDIC studies, primary risk factor for DN; hyperglycemia measured by hemoglobin A1c. In addition, female gender, late age of onset of diabetes in the prepubertal period, long diabetes duration, pubertal period with type 1 diabetes (T1DM), hypertension, high body mass index and genetic predisposition have been reported as risk factors for development of DN in children and adolescents. Method: We aimed to create a genetically based clinical risk scoring with polymorphisms in AFF3, CARS, CERS2, ERBB4, GLRA3, RAET1L, TMPO, ZMIZ1genes. Results: Of the 43 DN cases (Girl/Boy: 22/21) included in the study, 3 (6.9%) had a family history of consanguineous marriage between their parents, and 9 (20.9%) had a family history of T1DM. Of the cases, 23 (53.5%) were diagnosed with diabetic ketoacidosis, 14 (32.6%) with diabetic ketosis, and 6 (14%) with incidental T1DM. At the diagnosis of T1DM, the mean age was 8.34±3.53 years, body weight SDS: -0.17±1.07 SD, height SDS: 0.24±0.95 SD, body mass index (BMI) SDS: -0.54±1.35 SD. According to Tanner staging at the time of diagnosis, 32 (74.4%) of the cases were stage 1, 4 (9.3%) were stage 2, 3 (7%) were stage 3, 1 (2.3%) were stage 4 and 3 ( 7%) were stage 5 puberty. The systolic blood pressure percentile was 65.15±31.34 and the diastolic blood pressure percentile was 71.68±17.39 in the patients with nephropathy at the time of diagnosis. The mean age of detection of microalbuminuria (MA) in patients with diabetic nephropathy was 13.33±3.20, and the duration of diabetes was 4.95±3.99 years. MA was present at the time of diagnosis of T1DM in 5 cases (11.6%). The mean body weight SDS of DN cases at the time of diagnosis of MA was -0.26±0.95 SD, height SDS was 0.05±1.16 SD, and body mass index (BMI) SDS was -0.29±0.92 SD. The systolic blood pressure percentile was 70.54±28.59, and the diastolic blood pressure percentile was 75.57±18.24, at the time microalbuminuria was detected in cases with nephropathy. While the mean HbA1c value of the DN group was 8.74±1.99%, the HbA1 value of the T1DM group was 7.96±1.24%. In the cases in the DN and T1DM groups; Polymorphisms were investigated in AFF3, CARS, CERS2, ERBB4, GLRA3, RAET1L, TMPO, ZMIZ1, FRMD3 genes. The determined results were compared with randomly assigned healthy controls (50 cases). There was no difference in the frequency of polymorphism between DN, T1DM and healthy control groups. Conclusion: This study is a comprehensive study revealing the clinical and molecular features of diabetic nephropathy, and clinically the risk factors previously shown in the literature were confirmed. However, in this study, no difference was found between type diabetes and healthy control groups in polymorphisms known to be associated with diabetic nephropathy. This result may be due to a regional clustering in the study population.</p>