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

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

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

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

Distal arthrogryposis with variable clinical expression caused by TNNI2 mutation

Distal arthrogryposis (DA) is a clinically and genetically heterogeneous disorder with multiple joint contractures. We describe a female DA patient with hand and foot deformities, and right-sided torticollis. Using exome sequencing, we identified a novel TNNI2 mutation (c.485>A, p.Arg162Lys) in the patient and her father. The father has no typical DA but hip dysplasia. This may explain the clinical features of DA2B in this family, but with variable clinical expression

Analysis of leptin, adiponectin and adiponectin gene polymorphism and leptin receptor in obese children and adolescents

Background: The aim of this study was to determine serum levels of leptin and adiponectin of obese children to identify the influence of leptin receptor gene polymorphisms on leptin resistance and leptin levels, as well as the association between the polymorphisms of adiponectin gene and adiponectin levels.Materials and methods: A case-control study comparing a study group of 74 obese children (age 13.34±2.60 years) to a normal weight-age matched (age 13.39±2.64 years) control group of 69 children. In both groups, body mass index (BMI) and waist/hip circumference, systolic and diastolic blood pressure were measured. Also, the leptin and adiponectin levels, as well as glucose and lipid metabolism parameters, and highly sensitive C-reactive protein (hs-CRP) were measured. Insulin sensitivity was evaluated using fasting insulinemia and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). All subjects were tested for gene-tic polymorphisms in LEPRQ223R (rs1137101), ADIPOQ G276T (rs1501299) and ADIPOT45G (rs2241766).Results: The phenotypes of the obese children study group were significantly higher than in the control group in weight, BMI, waist/hip circumferences and systolic blood pressure (SBP) (P<0.001). We confirmed that in obese children the levels of leptin in the blood are increased and levels of adiponectin are decreased (P<0.001). The differences of the genotype distributions of leptin receptor (LEPRQ223R) and adiponectin (ADIPOG276T and ADIPOT45G) gene polymorphisms in the study group of obese chil-dren and a control group was not observed.Conclusion: In this study, we demonstrated increased leptin level and significantly decreased level of adiponectin in the obese children group compared with the control group. The results of the analysis of glucose metabolism and lipidogram between the two groups showed that insulin, HOMA-IR, and triglycerides, as well as hsCRP were increased and significantly different in the group of obese children compared to the control group, as expected. However, by including a significantly larger number of tested and control samples of both sexes and age-specific groups, with a larger number of tested SNPs, the genes investigated in this study would probably give better insight into a multicomplex disease such as obesity

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

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