scholarly journals Lack of mutations in the leptin receptor gene in severely obese children

2012 ◽  
Vol 56 (3) ◽  
pp. 178-183 ◽  
Author(s):  
Natasha Favoretto Dias ◽  
Ariana Ester Fernandes ◽  
Maria Edna de Melo ◽  
Heidi Lui Reinhardt ◽  
Cintia Cercato ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Receptor Gene ◽  
Hdl Cholesterol ◽  
Molecular Study ◽  
Serum Glucose ◽  
Clinical Feature ◽  
Coding Region ◽  
Obese Children ◽  
Exon 2 ◽  
Low Hdl

OBJECTIVE: To analyze the LEPR gene in obese children and to investigate the associations between molecular findings and anthropometric and metabolic features. SUBJECTS AND METHODS: Thirty-two patients were evaluated regarding anthropometric characteristics, blood pressure, heart rate, serum glucose, insulin, leptin levels, and lipid profile. The molecular study consisted of the amplification and automatic sequencing of the coding region of LEPR in order to investigate new mutations. RESULTS: We identified a high prevalence of metabolic disorders: impaired fasting glucose in 12.5% of the patients, elevated HOMA-IR in 85.7%, low HDL-cholesterol levels in 46.9%, high triglyceride levels in 40.6%, and hypertension in 58.6% of the patients. The molecular study identified 6 already described allelic variants: rs1137100 (exon-2), rs1137101 (exon-4), rs1805134 (exon-7), rs8179183 (exon-12), rs1805096 (exon-18), and the deletion/insertion of the pentanucleotide CTTTA at 3'untranslated region. CONCLUSIONS: The frequency of alleles observed in this cohort is similar to that described in the literature, and was not correlated with any clinical feature. The molecular findings in the analysis of the LEPR did not seem to be implicated in the etiology of obesity in these patients.

Impact of leptin and leptin-receptor gene polymorphisms on serum lipids in Japanese obese children

2010 ◽  
Vol 99 (8) ◽  
pp. 1213-1217 ◽  
Author(s):  
T Okada ◽  
T Ohzeki ◽  
Y Nakagawa ◽  
S Sugihara ◽  
O Arisaka ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Serum Lipids ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Obese Children ◽  
Receptor Gene Polymorphisms

scholarly journals Leptin Receptor Gene Variant rs11804091 Is Associated with BMI and Insulin Resistance in Spanish Female Obese Children: A Case-Control Study

2017 ◽  
Vol 18 (8) ◽  
pp. 1690 ◽  
Author(s):  
Josune Olza ◽  
Azahara Rupérez ◽  
Mercedes Gil-Campos ◽  
Rosaura Leis ◽  
Ramón Cañete ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Leptin Receptor ◽  
Case Control Study ◽  
Receptor Gene ◽  
Case Control ◽  
Gene Variant ◽  
Obese Children ◽  
Control Study

scholarly journals Comparison of Q223R leptin receptor polymorphism to the leptin gene expression in Greek young volunteers

2021 ◽  
Vol 8 (4) ◽  
pp. 301-310
Author(s):  
Panagiotis Halvatsiotis ◽  
◽  
Argyris Siatelis ◽  
Panagiotis Koulouvaris ◽  
Anthimia Batrinou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Rna Extraction ◽  
Genomic Region ◽  
Small Scale ◽  
Coding Region ◽  
Gender And Age ◽  
Study Results ◽  
Pcr Rflp

<abstract><sec> <title>Objective</title> <p>The objective of the present study was to identify the leptin gene expression and the leptin receptor polymorphisms in blood samples and to correlate gene expression values with anthropometric characteristics.</p> </sec><sec> <title>Methods</title> <p>Blood from 140 Greek young volunteers was subjected to polymerase chain reaction–restricted fragment length polymorphism (PCR–RFLP), for the genomic region of Q223R polymorphism at codon 223 in the leptin receptor gene (<italic>LEPR</italic>) coding region. RNA extraction, cDNA synthesis and Quantitative Real-Time PCR was performed for assessing the expression of the leptin gene (<italic>LEP</italic>).</p> </sec><sec> <title>Results</title> <p>Leptin gene was identified in all tested specimens and the gene was expressed in 88.9% of all volunteers with BMI &lt; 25. In addition, it was observed that gene expression is affected by various external factors, such as Body Mass Index (BMI), eating behavior, gender and age. It was also shown that as for the Q223R polymorphism (A to G) allele G occurs with a frequency of 100% in men with BMI &gt; 30 and 75.9% in men and 88.9% in women with BMI 25–30. Volunteers with BMI 25–30 who were homozygous on the G allele were 50% and 77.8% in men and women respectively. All subjects with a BMI &gt; 30 were homozygous on the G allele at 100%.</p> </sec><sec> <title>Conclusions</title> <p>In this small-scale study, results have shown that the leptin gene expression correlates with BMI and that the allele G in Q223R polymorphism is linked to overweight individuals.</p> </sec></abstract>

scholarly journals Missense mutations in exon 2 of the porcine leptin receptor gene and their associations with litter size and body weight

2009 ◽  
Vol 54 (No. 5) ◽  
pp. 210-216 ◽  
Author(s):  
C. Sun ◽  
L. Wang ◽  
D.F. Jiang ◽  
B. Zhang
Keyword(s):  
Litter Size ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Average Daily Gain ◽  
Live Weight ◽  
Gene Marker ◽  
Missense Mutations ◽  
Production Traits ◽  
Large White ◽  
Exon 2

Leptin receptor (<I>LEPR</I>) gene is regarded as a “candidate-gene” of production traits. The aims of this study were to detect polymorphisms of exon 2 within <I>LEPR</I> gene and to investigate their associations with production traits, litter size and live weight in Luchuan and Large White pig breeds. For this purpose, the single nucleotide polymorphisms (SNPs) of exon 2 within <I>LEPR</I> were detected using the PCR-SSCP procedure and their association with litter size and live weight was also analysed in Luchuan (<I>n</I> = 446) and Large White pigs (<I>n</I> = 405). The results showed that the C155T mutation was found in exon 2 of porcine <I>LEPR</I> gene in analyzed populations, which caused a missense mutation (Met to Thr). The different genotypes of this locus had the effects on total number of piglets born, born alive of the first (1<sup>st</sup>) and the first to the fourth (1<sup>st</sup>–4<sup>th</sup>) litters. The individuals with allele <I>A</I> had a higher number of total piglets born and a higher number of born alive piglets in the first litter (<I>P</I> < 0.05) while the differences in birth weight, weaning weight and average daily gain were not significant among different genotypes of this locus in analyzed populations. It implies that the exon 2 (Thr/Met) mutation of <I>LEPR</I> gene is a potential gene marker of pig reproduction. Therefore, it can be used in the marker-assisted selection (MAS) of pig breeding work.

scholarly journals Obesity in Children with Leptin Receptor Gene Polymorphisms

2021 ◽  
Vol 64 (3) ◽  
pp. 158-164
Author(s):  
Aleksandr Abaturov ◽  
Anna Nikulina
Keyword(s):  
Discriminant Analysis ◽  
Sequential Analysis ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Bioinformatic Analysis ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Multiple Discriminant Analysis ◽  
Obese Children ◽  
Nominal Data

Introduction: The study of single nucleotide polymorphisms (SNPs) of the leptin receptor gene (LEPR) based on next generation genomic sequencing (NGS) data is becoming an increasingly important aspect of diagnosis, treatment and prevention of both metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) phenotypes. Material and methods: 35 obese children 6-18 years old were examined by the NGS method with bioinformatic analysis. The main group (n = 18) was formed by children with MUO, according to the recommendations of the expert group of the National Heart, Lung, and Blood Institute. The control group (n = 17) was represented by children with MHO. Statistical methods were used: analysis of variance, Wald’s sequential analysis, Spearman’s correlation analysis, analysis of nominal data and multiple discriminant analysis. Results: 10 types of non-synonymous SNPs (rs3790435, rs1137100, rs2186248, rs70940803, rs79639154, rs1359482195, rs1137101, rs1805094, rs13306520, rs13306522) of the LEPR gene in obese children have been identified. Multiple discriminant analysis demonstrated that the following LEPR SNPs are of greatest importance in the development of MUO: rs3790435, rs13306522, rs13306520. Analysis of nominal data revealed significant differences in the groups for Copy number variation (CNV) rs3790435 of the LEPR gene. Wald’s analysis allowed us to identify 6 important predictors of MUO (І ≥ 0.5): 2 CNV rs3790435 (Relative Risk, RR = 2, Prognostic coefficient, PC = +2.76); male gender of the child (RR = 1.3, PC = +1.35); rs3790435 (RR = 1.9, PC = +2.76); hyperleptinemia more than 40.56 ng/ml (RR = 2, PC = +3); CNV rs1359482195 ≥ 3 (RR = 1.9, PC = +5.8); SNP of the LEPR gene ≥4 (RR = 3.8, PC = +5.8). Conclusion: Children with the genotype rs3790435 gene LEPR had signs of MUO more often.

scholarly journals Association of leptin receptor gene polymorphisms and meta-inflammation markers with metabolically unhealthy obesity in children

2021 ◽  
Vol 23 (5) ◽  
pp. 696-702
Author(s):  
А. Е. Abaturov ◽  
A. O. Nikulina
Keyword(s):  
Leptin Receptor ◽  
Receptor Gene ◽  
Strong Association ◽  
Main Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Inflammation Markers ◽  
Obese Children ◽  
Lepr Gene ◽  
Metabolically Unhealthy Obesity

The aim: to study the contribution of single-nucleotide polymorphisms (SNP) of the leptin receptor (LEPR) gene and meta-inflammation markers to the formation of metabolically unhealthy obesity (MUO) in children. Materials and methods. A total of 109 obese children aged 6–18 years were examined. Based on the recommendations of the National Heart, Lung, and Blood Institute (NHLBI), 2 observation groups were formed. The main group (n = 56) was represented by patients with MUO. The control group (n = 53) comprised children with metabolically healthy obesity (MHO). Serum levels of interleukin-1β (IL-1β) were measured using a chemiluminescent immunoassay (CLIA) method, interleukin-6, leptin, adiponectin – by enzyme-linked immunosorbent assay (ELISA) and the serum level of C-reactive protein were quantified by latex turbidimetric method (Synevo, Ukraine). The method of next-generation sequencing (NGS) (CeXGat, Germany) was used to identify LEPR SNP. Statistical methods were used: analysis of variance, Spearman’s correlation analysis and multiple discriminant analysis. Results. In obese children aged 6 to 18 years, there was an increase in pro-inflammatory adipokines IL-6 and leptin and a decrease in anti-inflammatory adiponectin. Statistically significant changes in these indicators were more expressed in the main group: IL-6 – 7.4 ± 0.5 pg/ml (ρ = 0.65; P ≤ 0.001); adiponectin – 3.9 ± 0.8 μg/ml (ρ = -0.27; P = 0.007) among all the children examined, leptin in girls – 47.8 ± 4.4 ng/ml (ρ = -0.28; P = 0.003) compared with the results of patients in the control group: IL-6 – 4.3 ± 0.3 pg/ml, adiponectin – 7.7 ± 2.4 μg/ml, leptin in girls – 32.5 ± 4.3 ng/ml, P ≤ 0.05. The most important in the development of MUO were the following SNP of the LEPR gene: rs3790435 (CiMUO = 0.939), rs2186248 (CiMUO = 0.862), P < 0.05. A strong correlation was found between MUO and serum IL-6 level (ρ = 0.7), LEPR SNP rs3790435 (ρ = 0.7), basal hyperinsulinemia (ρ = 0.72); Р ≤ 0.001. The risk of IL-6-dependent meta-inflammation in the presence of SNP rs3790435 of the LEPR gene: OR = 17.11; 95 % CI 2.8–20.4. Conclusions. Meta-inflammation in MUO is IL-6-dependent. Among the 10 SNPs of the LEPR gene that we identified, SNP rs3790435 of the LEPR gene has a strong association with the formation of MUO. SNP rs2186248 LEPR was described by us for the first time when it was found in 94.1 % of obese children, but it was characterized by the presence of a weak association with MUO.

scholarly journals Methylation status of leptin receptor gene promoter in obese children

2020 ◽  
Vol 95 (2) ◽  
pp. 86-91
Author(s):  
Katarzyna Jakubek-Kipa ◽  
Natalia Potocka ◽  
Marzena Skrzypa ◽  
Łukasz Dembinski ◽  
Izabela Zawlik ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Receptor Gene ◽  
Methylation Status ◽  
Gene Promoter ◽  
Obese Children

scholarly journals Seven SNPs in the Coding Sequence of Leptin Receptor Gene in Long-term Selected Japanese Quail Lines

2016 ◽  
Author(s):  
Kemal Karabağ ◽  
Sezai Alkan ◽  
Taki Karslı ◽  
Cengiz İkten ◽  
İnci Sahin ◽  
...  
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Amino Acid Sequences ◽  
Phenotypic Traits ◽  
Coding Region ◽  
Coding Sequence ◽  
Secondary Protein Structure

The objective of this study was to identify SNPs in the coding sequence of the leptin receptor gene and to test for their possible association with 20 economically advantageous traits in 15 generations of 2 selected (HBW and LBW) and a control of japanase quail. A 350-bp part of the leptin receptor coding region was amplified and sequenced and understood that the fragment contained 7 SNPs (GenBank:KP674322.1-KP674328.1) that were detected in 5 loci (T3216C, T3265C, T3265G, C3265G, T3303C, A3311G, and T3347C) in a total of 30 individuals. The T3216C and T3303C SNPs located at the end of the codon were synonymous and did not affect the presence of proline. However, phenylalanine, leucine and valine were produced when the T3265C, T3265G and C3265G SNPs, respectively, were present. Glutamine or arginine was produced when the A3311G SNP was A or G, respectively, and serine was produced when the T3347C SNP was C. Although codons and amino acid sequences changed due to the second SNP, the secondary protein structure was not changed. However, the fourth and fifth SNPs changed both the amino acid sequences and secondary protein structure. Pairing the SNP loci with phenotypic traits created haplogroups. When all individuals were evaluated together, some of the differences between the haplogroups were statistically significant (p<0.05; p<0.01). These results showed that both the sequence and structure of the leptin receptor gene could be altered by long-term selection. However, to achieve a more precise understanding of the role of leptin, entire coding sequences of leptin and the leptin receptor should be studied.

scholarly journals Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Marcello Scala ◽  
Midas Anijs ◽  
Roberta Battini ◽  
Francesca Madia ◽  
Valeria Capra ◽  
...  
Keyword(s):  
Missense Variant ◽  
Clinical Feature ◽  
Comparative Genomic ◽  
Speech Impairment ◽  
Coding Region ◽  
Exon 2 ◽  
Genetic Syndrome ◽  
Abnormal Movements ◽  
Intron 1 ◽  
Wide Range

Abstract Background Heterozygous variants in CNTNAP2 have been implicated in a wide range of neurological phenotypes, including intellectual disability (ID), epilepsy, autistic spectrum disorder (ASD), and impaired language. However, heterozygous variants can also be found in unaffected individuals. Biallelic CNTNAP2 variants are rarer and cause a well-defined genetic syndrome known as CASPR2 deficiency disorder, a condition characterised by ID, early-onset refractory epilepsy, language impairment, and autistic features. Case-report A 7-year-old boy presented with hyperkinetic stereotyped movements that started during early infancy and persisted over childhood. Abnormal movements consisted of rhythmic and repetitive shaking of the four limbs, with evident stereotypic features. Additional clinical features included ID, attention deficit-hyperactivity disorder (ADHD), ASD, and speech impairment, consistent with CASPR2 deficiency disorder. Whole-genome array comparative genomic hybridization detected a maternally inherited 0.402 Mb duplication, which involved intron 1, exon 2, and intron 2 of CNTNAP2 (c.97 +?_209-?dup). The affected region in intron 1 contains a binding site for the transcription factor FOXP2, potentially leading to abnormal CNTNAP2 expression regulation. Sanger sequencing of the coding region of CNTNAP2 also identified a paternally-inherited missense variant c.2752C > T, p.(Leu918Phe). Conclusion This case expands the molecular and phenotypic spectrum of CASPR2 deficiency disorder, suggesting that Hyperkinetic stereotyped movements may be a rare, yet significant, clinical feature of this complex neurological disorder. Furthermore, the identification of an in-frame, largely non-coding duplication in CNTNAP2 points to a sophisticated underlying molecular mechanism, likely involving impaired FOXP2 binding.

Sign in / Sign up

Export Citation Format

Share Document