Dataset Information

Serum Leptin Receptor and the rs1137101 Variant of the LEPR Gene Are Associated with Bladder Cancer.

ABSTRACT: Globally, bladder cancer (BC) is one of the ten most common tumors. Obesity is a worldwide problem associated with an increased BC risk. Considering that levels of leptin and/or its receptor are often deregulated in obese individuals, we hypothesized that they could contribute to BC. To test this hypothesis, we utilized a case-control study in which 116 patients with a confirmed diagnosis of BC and 116 controls were recruited. The serum levels of leptin and leptin receptor were measured. Patients and controls were also genotyped for SNPs in the LEP (rs7799039, rs791620, and rs2167270) and LEPR genes (rs1137100, rs1137101, and rs1805094). The univariate analysis indicated that BC patients had significantly higher levels of leptin and lower levels of leptin receptor (p < 0.05). Moreover, rs7799039 of LEP and rs1137101 of LEPR were associated with BC (p < 0.05). In the multivariate analysis, leptin receptor levels were protective (OR: 0.98, 95% CI = 0.97-0.99, p = 0.002) while the GG genotype of rs1137101 of LEPR increased BC risk (OR: 3.42, 95% CI = 1.27-9.20, p = 0.02). These findings highlight that lifestyle changes could be useful in preventing BC and that disturbances in energy metabolism could play a role in the pathobiology of BC.

SUBMITTER: Alfaqih MA

PROVIDER: S-EPMC10604959 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Serum Leptin Receptor and the rs1137101 Variant of the <i>LEPR</i> Gene Are Associated with Bladder Cancer.

Alfaqih Mahmoud A MA Elsalem Lina L Nusier Mohamad M Mhedat Khawla K Khader Yousef Y Ababneh Ebaa E

Biomolecules 20231009 10

Globally, bladder cancer (BC) is one of the ten most common tumors. Obesity is a worldwide problem associated with an increased BC risk. Considering that levels of leptin and/or its receptor are often deregulated in obese individuals, we hypothesized that they could contribute to BC. To test this hypothesis, we utilized a case-control study in which 116 patients with a confirmed diagnosis of BC and 116 controls were recruited. The serum levels of leptin and leptin receptor were measured. Patient ...[more]

PMID: 37892180

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Project description:Background: Type 2 diabetes mellitus (T2DM) is a multifaceted disease appropriate to elevated blood glucose levels resulting from decreased insulin and beta-cell activity. Using a case-control methodology, researchers have examined the relationship between polymorphisms in LEPR and T2DM in a population from south India.Materials and Methods: We conducted a genetic analysis of 311 participants, and results were accomplished using a case-control study, a meta-analysis of previous studies on LEPR was conducted, and type 2 diabetes genotype distribution across various geographical regions Malaysians, Chinese Han, Kuwait, Iran, Mongolia, and Han Chinese, Greece, Saudi, India (North India, Punjabi), (South India, Tamilnadu). The study involved 254 prospective investigations, and nine association studies were preferred according to preset criteria. Studies were assessed for quality using the Hardy-Weinberg equilibrium (HWE) and the Newcastle-Ottawa Scale (NOS). An analysis of the genetic models was conducted to determine their relationship, statistical analysis was utilized to calculate odds ratios (ORs) and matching 95% confidence intervals (CIs).Results: The LEPR-rs1137101 polymorphism in the case-control study was associated with a significant increase in the risk of type 2 diabetes. A meta-analysis revealed a connection between LEPR gene polymorphism (rs1137101) and type 2 diabetes risk. Investigators might gain a more profound thought on the significance of the identified genetic variation and its impact on the chance of developing type 2 diabetes by verifying and strengthening previously reported findings. The model of fixed effects was chosen due to the low heterogeneity, and significant associations were observed in the allelic (OR = 0.79, 95% CI [0.70-0.87]), homozygote (OR = 0.58, 95% CI [0.46-0.72]), dominant (OR = 0.66, 95% CI [0.56-0.79]), and recessive (OR = 0.83, 95% CI [0.71-0.96]) genetic models. A Begg's funnel plot and Egger's test indicated no publication bias. These findings suggest that the rs1137101 variant in the LEPR gene has been linked to a higher risk of T2DM.Conclusions: A larger sample size, however, is required for further research, and consideration of potential confounding factors is needed to validate these associations. Understanding the implications of LEPR gene polymorphisms in T2DM susceptibility may contribute to personalized treatment strategies for patients with T2DM.

Project description:The Gln233Arg (A>G; rs1137101) polymorphism of the leptin receptor gene (LEPR) has been investigated extensively and is reported to be associated with different metabolic states. In this investigation, we aimed to study the frequency of Gln233Arg genotypes and alleles in a group of Saudi women stratified by their body mass index (BMI), to correlate the LEPR genotypes with variations in anthropometric, lipid and hormonal parameters and to investigate conformational and structural variations in the mutant LEPR using molecular dynamic (MD) investigations. The study group included 122 Saudi women (normal weight = 60; obese = 62) attending the clinics for a routine checkup. Anthropometric data: height, weight, waist and hip circumference were recorded and fasting serum sample was used to estimate glucose, lipids, ghrelin, leptin and insulin. BMI, W/H ratio, and HOMA-IR values were calculated. Whole blood sample was used to extract DNA; exon 6 of the LEPR gene was amplified by PCR and sequencing was conducted on an ABI 3100 Avant Genetic Analyser. Molecular Dynamic Simulation studies were carried out using different softwares. The results showed the presence of all three genotypes of Gln233Arg in Saudi women, but the frequencies were significantly different when compared to reports from some populations. No differences were seen in the genotype and allele frequencies between the normal weight and obese women. Stratification by the genotypes showed significantly higher BMI, waist and hip circumference, leptin, insulin, fasting glucose and HOMA-IR and lower ghrelin levels in obese women carrying the GG genotype. Even in the normal weight group, individuals with GG genotype had higher BMI, waist and hip circumference and significantly lower ghrelin levels. The MD studies showed a significant effect of the Gln/Arg substitution on the conformation, flexibility, root-mean-square fluctuation (RMSF), radius of gyration (Rg) values, solvent-accessible surface area (SASA) and number of inter- and intra-molecular H-bonds. The results suggest that the structural changes brought about by the mutation, influence the signaling pathways by some unknown mechanism, which may be contributing to the abnormalities seen in the individuals carrying the G allele of rs1137101.

Dataset Information

Serum Leptin Receptor and the rs1137101 Variant of the LEPR Gene Are Associated with Bladder Cancer.

Publications

Serum Leptin Receptor and the rs1137101 Variant of the <i>LEPR</i> Gene Are Associated with Bladder Cancer.

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