Investigation of expression levels PCSK1(Proprotein convertase subtilisin/kexin type 1) and AGRP(Agouti related peptide)genes in patients with obesity admitted to Düzce University Pediatric Endocrinology Polyclinic

Obesity is a multifactorial disease which is very common all around the world and also it is afffected by environmental and genetic factors. Obesity is a risk factor for matabolic and cardiovascular complications and increases mortality. The role of the genetical factors in obesity is complex. In humans, obesity can be classified into two types; polygenic and monogenic obesity. In polygenic obesity there are many genetical factors and each of it contributes minimally however, in monogenic obesity is a rare condition case that was caused by a single gene. Monogenic obesity can be seen together with genetic syndromes or may be seen alone. Polygenic obesity is the most common genetic version of obesity and has multifactorial inheritance. Polygenic obesity occurs as a result of the interaction between genes and environmental factors. PC1 / 3 is encoded by the PCSK1 gene and it is an endoprotease enzyme which activates prohormone and proneopeptides. PC 1/3 activity enables the activation of several peptide hormone precursors which involved in the regulation of food intake, glucose homeostasis, and energy homeostasis. POMC protein hydrolysed by PC1 / 3 that has a role in reducing appetite. In humans, the aguti-associated peptide is encoded by the AGRP gene and is involved in increasing appetite, reducing metabolism and energy consumption. In this study, we aimed to determine the expression levels of PCSK1, AGRP genes in children and to evaluate whether there is any relationship between expression levels and demographic, clinical characteristics and laboratory results of the patients. Forty children with obesity who had at least one obese relative among their first-second and third degree relatives and 18 normal weighted control groups were compared. Total RNA was isolated from patients' peripheral blood samples. cDNA synthesis was performed and the expression level of PCSK1 and AGRP genes were determined by real time PCR (RT-PCR). There were a statistically significant difference in PCSK1 and AGRP expression levels between obese and control groups. There was a significantly relationship between PCSK1 gene expression level and body weight, BMI, waist circumference, hip circumference, triglyceride, insulin, TSH, HOMA-IR and delta bone age values at obese and control groups. There was a significantly relationship between AGRP gene expression level and BMI, waist circumference, hip circumference, insulin, TSH and HOMA-IR values at obese and control groups. According to our knowledge, there is any study in literature examining the PCSK1 gene expression level in obese patients and the results of our study supported that the dysfunction of the PCSK1 gene might cause obesity. AGRP helps to increase the appetite. Our investigation showed that, AGRP expression levels were found to be decreased in obese patients. These results suggested that not only appetite is effective in the development of obesity but also environmental factors might have a role. Keywords: child, obesity, PCSK1 gene, AGRP gene