ANALYSIS OF LEPTIN, ADIPONECTIN AND ADIPONECTIN GENE POLYMORPHISM AND LEPTIN RECEPTOR IN OBESE CHILDREN AND ADOLESCENTS

Abstract

CILJ: Utvrditi razine leptina i adiponektina u krvi pretile djece i adolescenata te saznati utječe li pojedini polimorfizam gena za sintezu leptinskog receptora na rezistenciju samog receptora na leptin i razinu leptina. Procijeniti utjecaj polimorfizama gena za adiponektin na njegovu razinu u krvi. MATERIJALI I METODE: Presječno istraživanje slučajeva i kontrola usporedbom ispitivane grupe od 30 pretile djece i adolescenata (dob 13.2±2.6 godina) sa kontrolnom skupinom od 30 djece normalne težinu usklađene dobi (dob 12.7±2.9 godina). U obje skupine izmjeren je indeks tjelesne mase (ITM) i opseg struka i bokova te sistolički i dijastolički krvni tlak. Izmjereni su i standardni metabolički parametri (GUK natašte, ukupni kolesterol i njegove frakcije, serumski trigliceridi). Osjetljivost na inzulin je procijenjena korištenjem inzulinemije natašte i HOMA-indeksa. Razine adiponektina i leptina određene su korištenjem ELISA metode. SNP-ovi su locirani PCR-RFLP metodom. REZULTATI: Serumska razina leptina bila je značajno veća (34.0±20.4 ng/mL u usporedbi s 9.1±6.4 ng/mL, p <0.001), a razina adiponektina značajno manja (3.56±1.1 ng/ml naspram 6.78±0.36 ng/mL, p <0.001) u skupini pretilih u odnosu na kontrolnu skupinu. LEPR SNP-ovi nisu značajno povezani s višim razinama leptina ni u skupini pretilih ni u kontrolnoj skupini (QR 43.3% za razliku od 63.3%; QQ 40% u odnosu na 26.7%; RR 16.7% usporedno sa 10%, p = 0.297). Nema značajne povezanost između ADIPOQ SNP-ova (TT 56.7% naspram 46.7%; GT 30% u odnosu na 43.3%; GG 13.3% spram 10%, p = 0.361) i razina adiponektina u ispitivanoj skupini u odnosu na kontrolnu skupinu. ZAKLJUČCI: Studija potvrđuje višu razinu cirkulirajućeg leptina i nižu koncentraciju adiponektina u ispitivanoj skupini pretile djece. U djece s pretilošću nije uočena povezanost genskih polimorfizama ADIPOQ s razinom adiponektina. Rezultati upućuju na to da genetička varijabilnost leptinskog receptora nije povezana s većim koncentracijama leptina. Pretpostavka je da su rezutati ove studije drugačiji od očekivanih su zbog malene veličine ispitivanog uzorka te bi dodatne studije s većim uzorcima trebale dati primjerenije rezultate.OBJECTIVES: To determine serum levels of leptin and adiponectin of obese children and adolescents and to identify the influence of the polymorphisms of leptin receptor gene on leptin resistance and leptin levels. Furthermore, to examine the association between the polymorphisms of adiponectin gene and adiponectin levels. PATIENTS AND METHODS: A case-control study comparing a study group of 30 obese children and adolescents (age 13.2±2.6 years) to a normal weight age matched (age 12.7±2.9 years) control group of 30 children. In both groups body mass index (BMI) and waist and hip circumference, systolic and diastolic blood pressure were mesured. Also, the classical metabolic parameters (fasting glycemia, total cholesterol and its fractions, serum triglycerides) were measured. Insulin sensitivity was evaluated using fasting insulinemia and HOMA-index. Adiponectin and leptin levels were determined using ELISA method. PCR-RFLP based assay was utilized to genotype SNPs. RESULTS: Serum level of leptin was significantly higher (34.0±20.4 ng/mL versus 9.1±6.4 ng/mL, p <0.001), while adiponectin levels were significantly lower (3.56±1.1 ng/mL versus 6.78±0.36 ng/mL, p <0.001) in the obese group compared to control group. LEPR SNPs were not significantly related to higher levels of leptin in the obese group nor in the non-obese (QR 43.3% versus 63.3%; QQ 40% versus 26.7%; RR 16.7% versus 10%, p=0.297). No significant association was identified between ADIPOQ SNPs (TT 56.7% versus 46.7%; GT 30% versus 43.3%; GG 13.3% versus 10%, p=0.361) and adiponectin levels in the case group compared to the control group. CONCLUSIONS: The study confirms higher levels of circulating leptin and lower concentrations of adiponectin in case group. In children with obesity was not observed association of the ADIPOQ gene polymorphisms with adiponectin levels. Results suggest that genetic variability in the leptin receptor is not associated with higher leptin concentrations. It is assumed these results were underpowered due to a small pooled sample size, and analysis of additional studies with larger sample sizes should provide further clarifications