Gene Gln223Arg Research Articles

The Arg/Arg genotype of leptin receptor gene Gln223Arg polymorphism may be an independent risk factor for nonalcoholic fatty liver disease.

Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined. In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P > .05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P = .036, odds ratio = 2.09 [95% CI = 1.31-5.95]). We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies.

Association of leptin receptor gene Gln223Arg polymorphism with insulin resistance and hyperglycemia in patients with metabolic syndrome.

Worldwide, there has been an increase in the incidence of metabolic syndrome. The search for genetic markers of this syndrome is ongoing. The leptin receptor has recently received attention. One of the polymorphisms (Gln223Arg) is possibly associated with the development of obesity and insulin resistance. However, the results of studies on this polymorphism remain equivocal. Gln223Arg polymorphism has not been studied previously in the Kyrgyz population. Thus, we aimed to investigate the possible association of the Gln223Arg polymorphism of the leptin receptor gene with metabolic syndrome components in the Kyrgyz population. 237 Kyrgyz subjects, aged 35-70 years, were studied. For the analysis anthropometric data, glucose, insulin, lipid spectrum, leptin were obtained. The genotype of the Gln223Arg leptin polymorphism was evaluated using TaqMan real-time PCR. The distribution of genotypes was as follows: Gln223Gln 46.4%, Gln223Arg 40.1%, Arg223Arg 13.5%. In the study no association was found with abdominal obesity, arterial hypertension, hypertriglyceridemia or low-density cholesterol levels. Relationships of Gln223Arg and Arg223Arg genotypes with insulin resistance (p < 0.03) were found. Gln223Arg polymorphism was associated with a higher level of glycemia (5.54 vs. 5.39 mmol/l, p < 0.05) and insulinemia (8.3 vs. 7.1 µIU/ml, p < 0.05). Correlation analysis showed that carriers of the Arg223 allele demonstrated a higher risk of insulin resistance (odds ratio (OR) = 1.83, 95% CI: 1.03-3.24; p < 0.03) than carriers of the Gln223 allele. Gln223Arg polymorphism of the leptin receptor gene may be a marker of predisposition to insulin resistance in the Kyrgyz population. Further studies are necessary to confirm these results in populations from other regions.

The Relationship of Leptin (+19) AG, Leptin (2548) GA, and Leptin Receptor Gln223Arg Gene Polymorphisms with Obesity and Metabolic Syndrome in Obese Children and Adolescents.

PurposeObesity is defined as the abnormal or excessive accumulation of fat over acceptable limits. Leptin is a metabolic hormone present in the circulation in amounts proportional to fat mass. Leptin reduces food intake and increases energy expenditure, thus regulating body weight and homeostasis. Various polymorphisms are present in the leptin gene and its receptor. These polymorphisms may be associated with obesity. This study aimed to show the association of leptin (+19) AG, leptin (2548) GA, and Gln223Arg leptin receptor polymorphisms with obesity and metabolic syndrome in Turkish children aged 6–17 years, and to conduct further investigations regarding the genetic etiology of obesity.MethodsA total of 174 patients diagnosed with obesity and 150 healthy children who were treated at Tokat Gaziosmanpaşa Medical School Hospital between September 2014 and March 2015 were included in this study. The ages of the children were between 6 and 17 years, and anthropometric and laboratory results were recorded. Genotyping of leptin (+19) AG, leptin (2548) GA, and leptin receptor Gln223Arg polymorphisms was performed by polymerase chain reaction.ResultsAn association between leptin receptor Gln223Arg gene polymorphism and obesity was detected.ConclusionFurther studies are needed to determine the role of genetic etiologies and to indicate the role of leptin signal transmission impairment in the pathogenesis of obesity. We hope that gene therapy can soon provide a solution for obesity.

Association of LEP G2548A and LEPR Gln223Arg Gene Polymorphism with Unexplained Infertility in North Indian Population

Association of LEP G2548A and LEPR Gln223Arg Gene Polymorphism with Unexplained Infertility in North Indian Population

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

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.

LEPR gene Gln223Arg polymorphism and type 2 diabetes mellitus: a meta-analysis of 3,367 subjects.

BackgroundThe Leptin receptor (LEPR) Gln223Arg gene polymorphism has been associated with an increased susceptibility to Type 2 diabetes mellitus (T2DM). Results from various studies, however, are inconsistent.Objective and methodsTo better elucidate the association of LEPR Gln223Arg gene polymorphism with T2DM in the Chinese population, a meta-analysis of 3,367 subjects from seven independent studies was performed. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) were evaluated by the fixed-effects model.ResultsA significant relationship between LEPR Gln223Arg gene polymorphism and T2DM in the Chinese population was found under allele (OR: 1.432, 95% CI: 1.211-1.694, P=2.67×10-5), dominant (OR: 1.466, 95% CI: 1.215-1.769, P=6.33×10-5), recessive (OR: 0.539, 95% CI: 0.303-0.960, P=0.036), heterozygous (OR: 0.700, 95% CI: 0.577-0.849, P=3.06×10-4), and homozygous (OR: 0.472, 95% CI: 0.265-0.839, P=0.011) genetic models.ConclusionsLEPR Gln223Arg gene polymorphism was associated with an increased risk of T2DM in the Chinese population. Therefore, Chinese carriers of the G allele of LEPR Gln223Arg gene polymorphism may be more susceptible to T2DM than the general population.

Leptin receptor polymorphism Gln223Arg (rs1137101) in oral squamous cell carcinoma and potentially malignant oral lesions.

The purpose of this study was to assess the LEPR gene Gln223Arg polymorphism (rs1137101) in oral squamous cell carcinoma (OSCC) and in potentially malignant oral lesions (PMOL) in comparison to normal oral mucosa in a Brazilian population. Smokers (n = 89) were selected from a representative sample of 471 individuals from the general population of Montes Claros, Brazil. Participants were age and gender matched to patients with OSCC (n = 25) and oral epithelial dysplasia (n = 25). We investigated the LEPR Gln223Arg polymorphism (A>G; rs1137101) in these groups. Genotype variants were assessed by RFLP-PCR, using MspI (HPAII) restriction endonuclease. The institutional review board of the Universidade Estadual de Montes Claros approved the study (process number 2667/2011). Written informed consent for this study was obtained from all participants. The GG genotype (Arg223Arg) appears to be the more relevant polymorphic variant in OSCC. It occurred, approximately, twice as frequently in OSCC patients than in the general population. In contrast, the A allele in its homozygosis form (Gln223Gln) is significantly associated with the development of PMOL; 80% of the samples from the PMOL group exhibit AA genotype. Our findings suggest new insights regarding LEPR gene variations in the development of OSCC and PMOL.

Leptin Receptor Gene Gln223Arg Polymorphism Is Not Associated with Hypertension: A Preliminary Population-Based Cross-Sectional Study.

Hypertension is responsible for high morbidity and mortality as one of the most important cardiometabolic risk factors. The aim of the study was to investigate whether the Gln223Arg in the leptin receptor (LEPR) influences the prevalence of hypertension. A cross-sectional study was carried out in individuals aged ≥ 18 years. Polymorphism identification was performed using PCR-RFLP analysis. Participants with blood pressure ≥ 140/90 mmHg or medication use were considered hypertensive. Frequencies, means, cross-tabulations, and multivariate models were produced to study differences in hypertension prevalence by genotypes. The study includes 470 participants. The frequency of GG polymorphism variant was 10.43%, 46.81% AG, and 42.77% AA. The distribution of hypertension frequency by LEPR genotypes was the following: AA 43.8%, AG 40.4%, and GG 40.8%; there were no significant differences between groups. Comparative analysis which used multivariate Poisson regression adjusted by many potential confounders (age, sex, schooling, smoking, alcohol intake, obesity, and family history of parental obesity) did not modify this result. In this large sample of population-based study, the association of the LEPR Gln223Arg gene polymorphism with hypertension was not observed.

No Association of Leptin Receptor Gene Gln223Arg Polymorphism with Capillary Glucose Levels: A Preliminary Population Base Cross-Sectional Study

The leptin receptor gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations. Therefore, the aim of the study was to investigate the associations of the leptin receptor gene Gln223Arg polymorphism (LEPR Gln223Arg) with high capillary glucose levels. Cross-sectional study with probabilistic sample was carried out in individuals aged ≥18 years in an urban area of Montes Claros, MG, Brazil. The capillary glucose was considered high when ≥140 mg/dL. The genotypes of LEPR Gln223Arg distribution were as the following: 10.43% GG (n=49), 46.81% AG (n=220), and 42.77% AA (n=201), and there were no prevalence differences between genders, (P=0.57). Multivariate-adjusted models showed that there is no association between the polymorphism LEPR Gln223Arg and capillary high levels of glucose even when adjusted for age, sex, smoking, schooling, and parental history of obesity. In conclusion, no association between the polymorphism LEPR Gln223Arg and elevated blood glucose levels was detected.

Effect of Leptin Receptor Mutation on the Development of Chronic Bronchitis

To investigate the effect of serum leptin level and leptin receptor (Lepr) genetic mutation on chronic bronchitis, we measured the serum leptin levels of 236 patients with chronic bronchitis and 107 healthy controls by ELISA, the genotype distribution of Lepr gene containing Gln223Arg polymorphic sites by the polymerase chain reaction-restriction fragment length polymorphism (RFLP) method, the levels of inflammatory markers in serum, and the concentration of neutrophils. We found that the GG genotype distribution and G gene frequency of Lepr gene Gln223Arg site of the patient group were higher than that in the control group. The serum high-sensitivity C-reactive protein and neutrophil granulocyte levels of the patient group were higher than those of the control group. But the leptin concentrations of those with GG genotype were lower than those with AA+AG genotype (P < .05). The mutation of Lepr gene Gln223Arg site may not directly influence the leptin level but could possibly advance the disease through inhibiting the biological effect of leptin.

Association of leptin receptor gene Gln223Arg polymorphism with susceptibility to colorectal cancer.

Leptin is a 16 kDa polypeptide hormone which secreted by adipose tissue and has an important role in energy balance, insulin pathway and inflammation, because of that it may play an important role in colorectal cancer (CRC). Leptin exerts its effect through the leptin receptor (LEPR) a member of the class I cytokine receptor family. We have investigated whether glutamine to arginine substitution (Gln223Arg) in exon 6 of the leptin receptor gene, has implications for susceptibility to CRC. Polymerase chain reaction (PCR) and restriction enzyme digestion (RFLP) was performed to evaluate the association between the Gln223Arg polymorphism of the LEPR and CRC risk in a case-control study in 346 subjects involving 173 cases with CRC and 173 controls. There was no statistically evidence of significant difference in genotype and allele frequencies between the cases with CRC and controls for the Gln223Arg polymorphism of LEPR, before or after adjusting for confounders (age, BMI, sex, and smoking status). Furthermore, no significant difference was observed between the CRC cases and controls by BMI, sex and smoking status. Our findings suggest that the LEPR Gln223Arg polymorphism is not associated with the risk of CRC in Iranian population.

Association of leptin receptor gene GIn223Arg polymorphism with insulin resistance in patients with metabolic syndrome

Objective To investigate the association of leptin receptor gene Gln223Arg polymorphism with metabolism syndrome and insulin resistance. Methods The genotypes of leptin receptor in 167 patients with metabolic syndrome and 216 healthy subjects were determined by polymerase chain reaction restriction fragment length polymorphism. The biochemical indicators were detected. Results The frequency of A alleles was significantly higher in patients with metabolic syndrome than in healthy subjects. The risk of metabolic syndrome in inviduals with allele A was 3. 302 folds of that with allele G( P<0.01 ). Compared with allele G, the patients withA allele had higher body mass index,blood pressure, blood glucose, insulin level, waist circumference, and more serious dyslipidemia. The risk of insulin resistance in patients with A allele was 3. 446 folds of that with allele G (P<0.01). Conclusions Leptin receptor gene Gln223Arg polymorphism is associated with an increased risk of metabolic syndrome and insulin resistance. Key words: Leptin receptor; Gene; Polymorphism,single nucleotide; Metabolic syndrome; Insulin resistance

Association Between the Gln223Arg Polymorphism of the Leptin Receptor and Metabolic Syndrome in Free-Living Community Elderly

Metabolic syndrome is a cluster of cardiovascular risk factors. Aging and gene-environmental interactions are involved in the pathophysiology of metabolic syndrome. The LEPR gene Gln223Arg polymorphism has been associated with energy metabolism and body weight. The association of the Gln223Arg polymorphism with metabolic syndrome was evaluated in a case-control study with elderly subjects (> or = 60 years old). The case-control groups were: (1) healthy group (HG), individuals without any cardio-metabolic diseases (CMD) or previous cardiovascular events (n = 64); (2) metabolic disorder group (MD), subjects with at least one metabolic disorder (hypertension, obesity, dyslipidemia, and impaired glucose tolerance, n = 306); and (3) metabolic syndrome group (MS) (n = 98). The Gln223Arg polymorphism of the LEPR gene was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) using Msp I endonuclease enzyme restriction. The mean age of the HG subjects was 70.12 +/- 7.7, and the MD and MS subjects were 69.7 +/- 6.4 and 69.68 +/- 5.0 years old, respectively. The MS group showed higher body mass index (BMI), waist circumference, systolic and diastolic blood pressure, glucose, cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) levels than did the HG individuals. The analysis showed differences in genotype frequencies: reduction in the Gln/Gln genotype and an excess of the Arg/Arg genotype in MD (chi(2) = 7.886, P = 0.019) and MS (chi(2) = 14.941, P = 0.001) when compared to the HG group. This study provides evidence for a role of the LEPR gene Gln223Arg polymorphism in predisposition to metabolic syndrome in the elderly.

No association of LEPR Gln223Arg polymorphism with leptin, obesity or metabolic disturbances in children

ObjectiveThe aim of the study was to investigate whether the Gln223Arg in the leptin receptor may influence body weight, leptin concentration, and metabolic parameters in children.Materials and methodsThe examined group included 101 obese children (58 girls and 43 boys) with BMI 31.41 ± 5.03 kg/m2 (BMI ≥ 2 SDS) and the control group consisted of 41 children with BMI 20.0 ± 0.80 kg/m2 (BMI < 1.0 SDS). Polymorphism identification was performed in total genomic DNA using PCRRFLP method.ResultsThe distribution of genotypes LEPR was the following: in the obese group: AA - 20.8%, AG-55.4%, GG-23.8%; in the control group AA-31.7%, AG-53.65%, GG-14.65%. Comparative analyses between AA homozygous children and carriers of G alleles did not confirm any relation between the analyzed polymorphism and BMI, leptin concentrations, and metabolic disturbances in children with obesity.ConclusionIn children with obesity we did not observe association of the LEPR Gln223Arg gene polymorphism with obesity, leptin, insulin resistance, and metabolic abnormalities.

Associations among Lipids, Leptin, and Leptin Receptor Gene Gin223Arg Polymorphisms and Breast Cancer in China

We evaluated the relationship among the leptin receptor (LEPR) gene Gln223Arg polymorphism, body mass index (BMI), waist and hip circumference ratio (WHR), dietary structure, lifestyle, and other biomarkers with breast cancer and determined whether they could be effective for the prevention and treatment of breast cancer. The Gln223Arg polymorphisms in the LEPR gene were investigated in blood deoxyribonucleic acid (DNA) available for 240 breast cancer cases and 500 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Leptin, insulin were determined by enzyme-linked immunosorbent assays. We found that the serum levels of leptin, insulin, triglyceride (TG), free cholesterol (FCH), apolipoprotain (APO) A1, and BMI were significantly higher in breast cancer cases than the controls, while physical activity was clearly less in breast cancer cases (P < 0.02 approximately P < 0.001, respectively). Moreover, there were significant association between the Gln223Arg genotype and breast cancer risk; homozygotes for AA and heterozygotes for AG,AG + GG genotypes had been proved to increase the risk of breast cancer, and their corresponding odds ratio were 7.14 (95% confidence interval [CI] = 1.92-25.64), 1.33(95% CI = 1.03-2.70), and 2.04 (95% CI = 1.09-3.82). Interestingly, logistic regression analysis showed that LEPR gene Gln223Arg polymorphism and elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB increased the risk of developing breast cancer, respectively. And, it also suggested that LEPR gene Gln223Arg polymorphisms, elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB should play a major role in the development of breast cancer.

Leptin receptor Gln223Arg variant is associated with a cluster of metabolic abnormalities in response to long-term overfeeding.

The role of the leptin receptor (LEPR) gene Gln223Arg polymorphism on the metabolic and body composition changes in response to overfeeding was studied. Twelve pairs of male monozygotic twins ate a 4.2 MJ day-1 energy surplus, 6 days week-1, during a period of 100 days. Overfeeding induced a significantly greater increase in glucose (P = 0.001 for percentage change) and insulin (P = 0.038) areas under the curve during oral glucose tolerance tests (OGTTs) in the GlnGln (n = 10) than in the GlnArg/ArgArg (n = 14) subjects. In addition, the GlnGln genotype was associated with a greater increase in plasma levels of leptin (P = 0.037) and total triglycerides (P = 0.003), as well as a greater decrease in high-density lipoprotein cholesterol (P = 0.010), than for the combined GlnArg/ArgArg genotypes. Body composition changes were not different between the genotypes. We conclude that the GlnGln subjects of the LEPR gene polymorphism are more susceptible to metabolic abnormalities when they are exposed to long-term positive energy balance. These findings provide new information on the genetic basis of individual differences in response to chronically elevated food intake.