Investigation of uridine diphosphate glucronyl transferase 1A1 (UGT1A1) gene by next generation sequenci̇ng in non-syndromic obese patients

Aim: Obesity prevalence is increasing worldwide and it is one of the most important health problems especially in developed countries. To the best of our knowledge, there are no studies in the literature which the UGT1A1 gene has been evaluated by the next generation sequence analysis method in non-syndromic obese patients.In this study, we aimed to determine the changes in the UGT1A1 gene by next generation sequence analysis in patients admitted to the Pediatric Polyclinics of Düzce University Hospital with the diagnosis of obesity. Methods: For the targeted molecular genetic diagnosis of the cases, DNAs isolated from the remaining waste blood which were obtained from whole blood samples for routine purposes and molecular genetic analysis was performed by using targeted next generation sequence analysis method. Results: Forty-five obese patients (76.3%) and 14 controls (23.7%) were included in the study.In terms of genetic changing in UGT1A1 gene, while 28 (62%) of the obese children had genetic changes, there were a genetic changes in 7 (50%) of the control group (p> 0.05). While only 2 genetic variations were detected in the control group, 7 additional variations were detected in the obese group. After classifying according to onset age of obesity (below and over the age of 2 years), we observed that 38.9% of the patients with early onset obesity and 77.8% of the patients with late onset obesity (at any age over 2 years of age) had UGT1A1 gene variations. Both total and direct bilirubin levels were significantly lower in children with obesity under 2 years of age. Conclusion: In the late-onset group, the genetic changes in the UGT1A1 gene were evaluated by logistic regression analysis and we showed that these genetic changes increased the risk of late onset obesity 3 times (3.42 % 95 CI, 0.15-5.11 p:0.000). However, considering the protective effect of bilirubin, especially for early-onset obesity, follow-up should be performed more carefully because of lower levels of bilirubin. Our study is the first study showing age-related changes between the diversity of UGT1A1 gene polymorphisms, bilirubin levels and onset age of obesity.