scholarly journals The Q223R Polymorphism of the Leptin Receptor Gene as a Predictor of Weight Gain in Childhood Obesity and the Identification of Possible Factors Involved

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 560
Author(s):  
Helena Marcos-Pasero ◽  
Elena Aguilar-Aguilar ◽  
Gonzalo Colmenarejo ◽  
Ana Ramírez de Molina ◽  
Guillermo Reglero ◽  
...  
Keyword(s):  
Weight Gain ◽  
Childhood Obesity ◽  
Leptin Receptor ◽  
Linear Models ◽  
Receptor Gene ◽  
Lifestyle Factors ◽  
Nucleotide Polymorphisms ◽  
Rapid Weight Gain ◽  
Activity Data ◽  
Weight Growth

(1) Background: Childhood rapid weight gain during development has been postulated as a predictor of obesity. The objective of this study was to investigate the effect of single nucleotide polymorphisms (SNPs) on the annual weight gain and height growth, as well as identifying possible lifestyle factors involved. (2) Methods: As part of the GENYAL study, 221 children (6–8 years old) of Madrid (Spain) were enrolled. A total of 11 SNPs associated with high childhood body mass indexes (BMIs) were assessed. Anthropometric measurements, dietary and physical activity data, were collected in 2017 and 2018. Bonferroni-corrected linear models were used to fit the data. (3) Results: A significant association between the Q223R LEPR and the weight growth was found, showing a different behavior between GA and GG genotypes (p = 0.001). Regarding lifestyle factors, an interaction between Q223R genotypes and total active weekly hours/week to predict the weight growth (kg/year) was observed (p = 0.023). In all the genotypes, a beneficial effect against rapid weight growth was observed, but the effect size of the interaction was much more significant in homozygous (GG) minor homozygous (β = −0.61 (−0.95, −0.26) versus heterozygous (AG) and wild-type homozygous (AA) genotypes (β = −0.07 (−0.24, 0.09) and β = −0.12 (−0.32, 0.08), respectively). (4) Conclusions: These results may contribute to more personalized recommendations to prevent childhood obesity.

scholarly journals Genetic Variation in the Leptin Receptor Gene, Leptin, and Weight Gain in Young Dutch Adults

2003 ◽  
Vol 11 (3) ◽  
pp. 377-386 ◽  
Author(s):  
Caroline T.M. van Rossum ◽  
Barbara Hoebee ◽  
Marleen A. van Baak ◽  
Monica Mars ◽  
Wim H.M. Saris ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Weight Gain ◽  
Leptin Receptor ◽  
Receptor Gene

scholarly journals Genetic aspects of metabolic disorders in pregnant women with pathological weight gain

2019 ◽  
Vol 10 (3) ◽  
pp. 271-275
Author(s):  
S. O. Ostafiichuk
Keyword(s):  
Weight Gain ◽  
Pregnant Women ◽  
Leptin Receptor ◽  
Metabolic Diseases ◽  
Receptor Gene ◽  
Insulin Level ◽  
Late Pregnancy ◽  
Serum Levels ◽  
Leptin Resistance ◽  
Enzyme Linked Immunosorbent Assay

Polymorphism of the leptin receptor gene (LEPR) has been shown to be linked to obesity-related metabolic markers and phenotype. Therefore, we hypothesized that the Gln233Arg LEPR polymorphism is related to metabolic changes in pregnancy and the risk of excessive gestational weight gain (GWG). A total of 97 pregnant women with a singleton gestation were enrolled from April 2016 until December 2018. Genetic variants of LEPR were analyzed by real-time polymerase chain reaction, leptin by enzyme-linked immunosorbent assay, lipid profile, and carbohydrate status were assessed in the first, and third trimesters of pregnancy. The recommended GWG was diagnosed in 34.0%, insufficient in 19.6%, and excessive in 46.4% patients. Statistical analysis revealed that 20.6% patients were with AA genotype, 50.5% – AG genotype, and 28.9% – GG genotype. The frequency of GG-alleles carriers of the LEPR Gln233Arg gene in the group of excessive GWG patients was 3 times higher compared to recommended GWG patients. Thus, the inheritance of pathological G-homozygotes increases the risk of excessive weight gain by 7 times, compared to carriers of the AA genotype. LEPR GG polymorphism was significantly associated with high levels of triglycerides, total cholesterol, lipoprotein low and very low density, and leptin compared to homozygous А-carriers in the third trimester of pregnancy. In pregnant women with GG polymorphism, the glucose level, insulin level, and HOMO-IR index were significantly increased compared to women with AA genotype in late pregnancy. In the group with excessive GWG, the presence of GG-alleles of the LEPR gene was accompanied by a higher level of hyperleptinemia, compared to carriers of AA-genotype. Inheritance of pathological G-homozygotes was associated with hyperlipidemia, leptin resistance with high leptin serum levels, and increased insulin resistance, which was especially manifested in excessive GWG. In our opinion, excessive GWG can be seen as a marker of the mother's genotype and genetic predisposition to the development of metabolic diseases after delivery.

scholarly journals Polygenic risk score based on weight gain trajectories is predictive of childhood obesity

2019 ◽  
Author(s):  
Sarah J. C. Craig ◽  
Ana M. Kenney ◽  
Junli Lin ◽  
Ian M. Paul ◽  
Leann L. Birch ◽  
...  
Keyword(s):  
Weight Gain ◽  
Childhood Obesity ◽  
Risk Score ◽  
Genetic Variants ◽  
Association Studies ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide

AbstractObesity is highly heritable, yet only a small fraction of its heritability has been attributed to specific genetic variants. These variants are traditionally ascertained from genome-wide association studies (GWAS), which utilize samples with tens or hundreds of thousands of individuals for whom a single summary measurement (e.g., BMI) is collected. An alternative approach is to focus on a smaller, more deeply characterized sample in conjunction with advanced statistical models that leverage detailed phenotypes. Here we use novel functional data analysis (FDA) techniques to capitalize on longitudinal growth information and construct a polygenic risk score (PRS) for obesity in children followed from birth to three years of age. This score, comprised of 24 single nucleotide polymorphisms (SNPs), is significantly higher in children with (vs. without) rapid infant weight gain—a predictor of obesity later in life. Using two independent cohorts, we show that genetic variants identified in early childhood are also informative in older children and in adults, consistent with early childhood obesity being predictive of obesity later in life. In contrast, PRSs based on SNPs identified by adult obesity GWAS are not predictive of weight gain in our cohort of children. Our research provides an example of a successful application of FDA to GWAS. We demonstrate that a deep, statistically sophisticated characterization of a longitudinal phenotype can provide increased statistical power to studies with relatively small sample sizes. This study shows how FDA approaches can be used as an alternative to the traditional GWAS.Author SummaryFinding genetic variants that confer an increased risk of developing a particular disease has long been a focus of modern genetics. Genome wide association studies (GWAS) have catalogued single nucleotide polymorphisms (SNPs) associated with a variety of complex diseases in humans, including obesity, but by and large have done so using increasingly large samples-- tens or even hundreds of thousands of individuals, whose phenotypes are thus often only superficially characterized. This, in turn, may hide the intricacies of the genetic influence on disease. GWAS findings are also usually study-population dependent. We found that genetic risk scores based on SNPs from large adult obesity studies are not predictive of the propensity to gain weight in very young children. However, using a small cohort of a few hundred children deeply characterized with growth trajectories between birth and two years, and leveraging such trajectories through novel functional data analysis (FDA) techniques, we were able to produce a strong childhood obesity genetic risk score.

scholarly journals Genome-wide analyses reveal a strong association between LEPR gene variants and body fat reserves in ewes

2021 ◽  
Author(s):  
Tiphaine Macé ◽  
Eliel Gonzalez-Garcia ◽  
Didier Foulquié ◽  
Fabien Carrière ◽  
Julien Pradel ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Body Condition Score ◽  
Receptor Gene ◽  
Strong Association ◽  
Significant Snps ◽  
Chromosome 1 ◽  
Nucleotide Polymorphisms ◽  
Fat Reserves ◽  
Genome Wide ◽  
Pregnancy And Lactation

Among the adaptive capacities of animals, the management of energetic body reserves (BR) through the BR mobilization and accretion processes (BR dynamics, BRD) has become an increasingly valuable attribute for livestock sustainability, allowing animals to cope with more variable environments. BRD has previously been reported to be heritable in ruminants. In the present study, we conducted genome-wide studies (GWAS) in sheep to determine genetic variants associated with BRD. BR levels and BR changes over time were obtained through body condition score measurements at eight physiological stages throughout each productive cycle in Romane ewes (n=1034) and were used as phenotypes for GWAS. After quality controls and imputation, 48,513 single nucleotide polymorphisms (SNP) were included in the GWAS. Among the QTLs identified, a major QTL associated with BR levels during pregnancy and lactation was identified on chromosome 1. In this region, several significant SNPs mapped to the leptin receptor gene (LEPR), among which one SNP mapped to the coding sequence. The point mutation induces the p.P1019S substitution in the cytoplasmic domain, close to tyrosine phosphorylation sites. The frequency of the SNP associated with increased BR levels was 32%, and the LEPR genotype explained up to 5% of the variance of the trait. These results provide strong evidence for involvement of LEPR in the regulation of BRD in sheep and highlight it as a major candidate for improving adaptive capacities.

scholarly journals Fine mapping of porcine chromosome 6 QTL and LEPR effects on body composition in multiple generations of an Iberian by Landrace intercross

2005 ◽  
Vol 85 (1) ◽  
pp. 57-67 ◽  
Author(s):  
C. ÓVILO ◽  
A. FERNÁNDEZ ◽  
J. L. NOGUERA ◽  
C. BARRAGÁN ◽  
R. LETÓN ◽  
...  
Keyword(s):  
Body Composition ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Chromosome 6 ◽  
Nucleotide Polymorphisms ◽  
Fat Percentage ◽  
Muscle Area ◽  
Eye Muscle ◽  
Coding Regions ◽  
Narrow Region

The leptin receptor gene (LEPR) is a candidate for traits related to growth and body composition, and is located on SSC6 in a region where fatness and meat composition quantitative trait loci (QTL) have previously been detected in several F2 experimental designs. The aims of this work were: (i) to fine map these QTL on a larger sample of animals and generations (F3 and backcross) of an Iberian×Landrace intercross and (ii) to examine the effects of LEPR alleles on body composition traits. Eleven single nucleotide polymorphisms (SNPs) were detected by sequencing LEPR coding regions in Iberian and Landrace pig samples. Three missense polymorphisms were genotyped by pyrosequencing in 33 F0, 70 F1, 418 F2, 86 F3 and 128 individuals coming from the backcross of four F2 males with 24 Landrace females. Thirteen microsatellites and one SNP were also genotyped. Traits analysed were: backfat thickness at different locations (BFT), intramuscular fat percentage (IMFP), eye muscle area (EMA), loin depth (LOD), weight of shoulder (SHW), weight of ribs (RIBW) and weight of belly bacon (BBW). Different statistical models were applied in order to evaluate the number and effects of QTL on chromosome 6 and the possible causality of the LEPR gene variants with respect to the QTL. The results support the presence of two QTL on SSC6. One, at position 60–100 cM, affects BFT and RIBW. The other and more significant maps in a narrow region (130–132 cM) and affects BFT, IMFP, EMA, LOD, SHW, RIBW and BBW. Results also support the association between LEPR alleles and BFT traits. The possible functional implications of the analysed polymorphisms are considered.

Mutations in the leptin receptor gene associated with delayed onset of puberty are also associated with decreased ovulation and lambing rates in prolific Davisdale sheep

2016 ◽  
Vol 28 (9) ◽  
pp. 1318 ◽  
Author(s):  
Jennifer L. Juengel ◽  
Michelle C. French ◽  
Anne R. O'Connell ◽  
Sara J. Edwards ◽  
Avijit Haldar ◽  
...  
Keyword(s):  
Reproductive Performance ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Reproductive Traits ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Partial Failure ◽  
Delayed Onset ◽  
Service Conception

The aim of this study was to determine if single nucleotide polymorphisms (SNPs) in the leptin receptor (LEPR) gene associated with delayed onset of puberty are associated with changes in other reproductive traits in adult ewes. The ovulation rate of ewes homozygous for the SNPs was ~15% lower (P < 0.001) than either wild-type or heterozygous ewes. First-service conception rate was also affected, being ~12% lower (P < 0. 01) in ewes homozygous for the LEPR SNPs than their wild-type or heterozygous contemporaries. Partial failure of multiple ovulations was also increased (P < 0.01) in ewes that ovulated three ova that were either heterozygous or homozygous for the mutations. Ewes homozygous for the mutations in LEPR had on average 0.2 fewer lambs at mid-pregnancy and at birth compared with the wild-type or heterozygous ewes (P < 0.01). Thus, mutations in LEPR were strongly associated with poorer reproductive performance in Davisdale ewes, which is likely to be linked to both a reduced number of ova available for fertilisation and an increased number of ewes failing to become pregnant. Increased partial failure of multiple ovulations in ewes with high ovulation rates (i.e. 3 or greater) may also contribute to the poor reproductive performance.

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 Pharmacogenetics of antipsychotic-induced side effects

2009 ◽  
Vol 11 (4) ◽  
pp. 405-415 ◽  
Keyword(s):  
Weight Gain ◽  
Side Effects ◽  
Serotonin Receptor ◽  
Antipsychotic Drugs ◽  
Receptor Gene ◽  
Effect Sizes ◽  
Patient Specific ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Primary Focus

Currently available antipsychotic drugs (APDs) carry significant though highly variable, liability to neurologic and metabolic side effects. Pharmacogenetics approaches offer the possibility of identifying patient-specific biomarkers for predicting risk of these side effects. To date, a few single nucleotide polymorphisms (SNPs) in a handful of genes have received convergent support across multiple studies. The primary focus has been on SNPs in dopamine and serotonin receptor genes: persuasive meta-analytic evidence exists for an effect of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardive dyskinesia (TD) and for an effect of variation at the 5-HT2C receptor gene (HTR2C) for liability to APD-induced weight gain. However, effect sizes appear to be modest, and pharmacoeconomic considerations have not been sufficiently studied, thereby limiting clinical applicability at this time. Effects of these genes and others on risk for TD, extrapyramidal side effects, hyperprolactinemia, and weight gain are reviewed in this article.

scholarly journals Childhood obesity: rapid weight gain in early childhood and subsequent cardiometabolic risk

2020 ◽  
Vol 29 (4) ◽  
pp. 135-142 ◽  
Author(s):  
Osamu Arisaka ◽  
Go Ichikawa ◽  
Satomi Koyama ◽  
Toshimi Sairenchi
Keyword(s):  
Early Childhood ◽  
Weight Gain ◽  
Childhood Obesity ◽  
Cardiometabolic Risk ◽  
Rapid Weight Gain
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