Polymorphism in leptin receptor gene was associated with obesity in Yogyakarta, Indonesia

Hastuti, Pramudji; Zukhrufia, Izza; Padwaswari, Made Harumi; Nuraini, Afifah; Sadewa, Ahmad Hamim

doi:10.1016/j.ejmhg.2015.12.011

Cited by 18 publications

(11 citation statements)

References 31 publications

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“…In our study population, the frequency of A allele was higher than the frequency of G allele and it might be the reason that we observed no significant correlation between G allele and obesity or overweight. However, such mutations are extremely rare and data in literature concerning the association between Lys109Arg polymorphism and obesity are controversial among different ethnic populations (15,17,18). If we could study more samples from different ethnic groups of Iranian population, G allele or GG genotype would have a significant correlation with obesity or overweight.…”

Section: Discussionmentioning

confidence: 99%

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Association of Leptin Receptor Gene Gln223Arg and lys109Arg Polymorphisms with Obesity and Overweight in an Iranian Young Population

2017

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Background: Obesity is an energy imbalance disorder that happens due to deficiency of energy intake and consumption. Leptin is an important hormone that regulates energy expenditure. Leptin through its receptors located in the hypothalamus regulates appetite and energy consumption. Objectives: In this study we tried to determine the association of leptin receptor (LEPR) gene polymorphisms (rs1137101), Lys223Arg and Gln109Arg (rs1137100), with overweight and obesity. Methods: We examined the two polymorphisms in 240 subjects consisting of obese, overweight, low-weight, and normal weight (as control) subjects among students of Zanjan Islamic Azad University. For Genotyping, we used PCR-RFLP. Statistical analysis was performed using t-test and chi-square test to show any significant difference between the groups. Results: There was no significant difference in allelic and genotypic frequency of Gln109Arg polymorphism (by A > G substitution) between our study groups. In Lys223Arg polymorphism by A > G substitution, the frequency of AG genotype was higher in the normal group, and the frequency of AA genotype was higher in the obese and overweight groups; but, there was no significant difference in GG genotype and allelic frequency (P < 0.05). Conclusions: In our population, Lys223Arg polymorphism of LEPR gene was associated with obesity; Gln 223 of leptin receptor gene was located in the extra cellular part of receptor and substitution of Glu by Arg in this position might affect leptin signaling. Lys/Arg heterozygote might have protective effects.

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Section: Discussionmentioning

confidence: 99%

“…Due to the low frequency of G allele in our study group, we could not investigate the exact correlation of G allele or GG genotypes with obesity. In some other ethnic groups, researchers reported Gln223Arg polymorphism could have a critical role in obesity and overweight (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Association of Leptin Receptor Gene Gln223Arg and lys109Arg Polymorphisms with Obesity and Overweight in an Iranian Young Population

2017

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“…Besides these genes, SNPs in other obesity-related genes were observed in one or more of the obesity donors, but not in all. Several obesity-related SNPs in LEPR genes, such as rs1137101 (Furusawa et al, 2010), rs1805094 (Rojano-Rodriguez et al, 2016), and rs1137100 (Hastuti et al, 2016), were observed. PPARG SNP rs3856806 was observed in two samples, which have been associated with risk of obesity and type 2 diabetes (Lv et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Super-Obese Patient-Derived iPSC Hypothalamic Neurons Exhibit Obesogenic Signatures and Hormone Responses

et al. 2018

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The hypothalamus contains neurons that integrate hunger and satiety endocrine signals from the periphery and are implicated in the pathophysiology of obesity. The limited availability of human hypothalamic neurons hampers our understanding of obesity disease mechanisms. To address this, we generated human induced pluripotent stem cells (hiPSCs) from multiple normal body mass index (BMI; BMI ≤ 25) subjects and super-obese (OBS) donors (BMI ≥ 50) with polygenic coding variants in obesity-associated genes. We developed a method to reliably differentiate hiPSCs into hypothalamic-like neurons (iHTNs) capable of secreting orexigenic and anorexigenic neuropeptides. Transcriptomic profiling revealed that, although iHTNs maintain a fetal identity, they respond appropriately to metabolic hormones ghrelin and leptin. Notably, OBS iHTNs retained disease signatures and phenotypes of high BMI, exhibiting dysregulated respiratory function, ghrelin-leptin signaling, axonal guidance, glutamate receptors, and endoplasmic reticulum (ER) stress pathways. Thus, human iHTNs provide a powerful platform to study obesity and gene-environment interactions.

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“…Yiannakouris et al (19) showed that Q223R polymorphism was associated with obesity and predicts approximately 5% of body weight and body composition variability in the Greek population. Hastuti et al (20) reported that Q223R polymorphism and phenotype of obesity was associated in the Yogyakarta population. Lv et al (21) analyzed that there was an association between Gln233Arg polymorphism and OSA risk in European but not for Asian populations (22).…”

Section: Introductionmentioning

confidence: 99%

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2017

Eur J Biol

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Given the prominence of obesity in the OSAS phenotype, the genetic underpinning of obesity is highly relevant to the study of the genetic basis of OSAS. Furthermore, a number of genes implicated in obesity Eur J Biol 2017; 76(2) ABSTRACTLeptin is derived from an adipocyte and acts through the leptin receptor (LEPR). Gln223Arg polymorphism of the LEPR gene is thought to be associated with impaired signaling capacity of LEPR and with higher mean circulating levels of leptin and obesity; therefore, it may contribute to the pathogenesis of obstructive sleep apnea syndrome (OSAS). The aim of this study was to investigate the frequency of distribution of LEPR gene polymorphism (Gln223Arg) in OSAS patients in relation to polysomnographic traits and phenotype. In total, 230 men (152 OSAS patients and 78 controls) were included in the study. All participants were evaluated by polysomnography in addition to anthropometric, metabolic, and hemodynamic variables. The relationship between these phenotypes and polymorphism of the LEPR gene was investigated by PCR-RFLP. There was no difference between the genotype frequencies of the Gln223Arg polymorphism in the OSAS and control groups. However, OSAS patients carrying the R allele (RR and QR genotypes) had significantly lower Body Mass Index (BMI) than those carrying the Q allele (QQ). OSAS patients with the RR genotype had a significantly lower diastolic blood pressure value than those with the QQ and QR genotypes. When all participants were grouped by blood pressure, the genotype frequency of RR individuals was more prevalent among normotensive men compared to hypertensive men. Gln223Arg polymorphism of LEPR does not seem to be associated with OSAS. This polymorphism may, however, predispose the carrier to reduced BMI and blood pressure. Further studies are needed to unveil the genetic basis of OSAS pathophysiology.

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Polymorphism in leptin receptor gene was associated with obesity in Yogyakarta, Indonesia

Cited by 18 publications

References 31 publications

Association of Leptin Receptor Gene Gln223Arg and lys109Arg Polymorphisms with Obesity and Overweight in an Iranian Young Population

Association of Leptin Receptor Gene Gln223Arg and lys109Arg Polymorphisms with Obesity and Overweight in an Iranian Young Population

Super-Obese Patient-Derived iPSC Hypothalamic Neurons Exhibit Obesogenic Signatures and Hormone Responses

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