LEPR polymorphisms and haplotypes in Mexican patients with colorectal cancer / Polimorfismos y haplotipos del gen LEPR en pacientes mexicanos con cáncer colorrectal

Abstract Introduction: Obesity and colorectal cancer could be linked by adipocytokines, which are proteins associated with cell proliferation. High levels of the adipocytokine leptin promote the development of colorectal cancer through its receptor. Objective: To determine the association between c.326A>G and c.668A>G LEPR gene polymorphisms and colorectal cancer. Materials and methods: DNA was extracted from the peripheral blood of 147 patients with sporadic colorectal cancer and 134 healthy people. Genotypes were obtained by PCR- RFLP and the association was determined by the odds ratio (OR) test using the SPSS™, version 10.0, program. Haplotype frequencies and linkage disequilibrium were estimated by the Arlequin, version 3.5, software. Results: Both polymorphisms were in Hardy-Weinberg equilibrium. Only the c.326A>G heterozygous genotype revealed an increased risk for colorectal cancer development (OR=1.81, 95% CI=1.04-3.16, p=0.04). The AG haplotype showed a significant association with colorectal cancer (OR=0.58, 95% CI=0.35-0.96, p<0.03). Linkage disequilibrium between the variants was only evident for the patients group (r2=0.36). Conclusion: Our results suggest that AG individuals heterozygous for the c.326A>G LEPR variant have a higher risk of colorectal cancer development whereas the AG haplotype (c.326A/c.668G) has a protective effect in the Mexican population.

Resumen Introducción. La relación entre la obesidad y el cáncer colorrectal podría estar dada por las adipocitocinas, proteínas asociadas con la proliferación celular. Los niveles elevados de la adipocitocina leptina promueven el desarrollo del cáncer colorrectal a través de su receptor. Objetivo. Determinar la asociación de los polimorfismos c.326A>G y c.668A>G del gen LEPR con el cáncer colorrectal. Materiales y métodos. A partir de sangre periférica, se extrajo el ADN de 147 pacientes con cáncer colorrectal esporádico y de 134 personas sanas. La genotipificación se hizo mediante PCR-RFLP y la asociación se determinó por la odds ratio (OR) en el programa SPSS™, versión 10.0. Las frecuencias haplotípicas y el desequilibrio de ligamiento se estimaron utilizando el programa Arlequin, versión 3.5. Resultados. Ambos polimorfismos estaban en equilibrio de Hardy-Weinberg. Solo el genotipo heterocigoto c.326A>G reveló un mayor riesgo de desarrollar cáncer colorrectal (OR=1,81; IC95% 1,04-3,16; p=0,04). El haplotipo AG mostró una asociación significativa con este cáncer (OR=0,58; IC95% 0,35-0,96; p≤0,03) y el desequilibrio de ligamiento entre las variantes fue evidente únicamente en el grupo de pacientes (r2=0,36). Conclusión. Los resultados sugieren que los individuos heterocigotos con el haplotipo AG para la variante c.326A>G en el gen LEPR tenían un mayor riesgo de desarrollar cáncer colorrectal, en tanto que el haplotipo AG (c.326A/c.668G) tenía un efecto protector en la población mexicana.

Expression and significance of serum leptin and lung tissue leptin receptor in rats with pulmonary arterial hypertension induced by monocrotaline / 重庆医学

Objective To study the significance of leptin and its receptor(OB-R) in the occurrence and development of pulmonary arterial hypertension(PAH) induced by monocrotaline(MCT).Methods Fifteen SD rats were divided into the control group(n=5) and two experimental groups(n=10).The experimental groups were intraperitoneally injected by MCT for constructing the PAH model and the control group was injected by the same dose of solvent groups.The venous blood was extracted at 2,4 weeks after MCT injection in the two experimental groups.The mean pulmonary artery pressure(mPAP) and right ventricular hypertrophy index(RVHI) were measured and then the lung tissue was removed.The pathological change of lung blood vessels was observed.The expression of serum leptin was detected by ELISA.The expression of OB-R in lung tissue was tested by Western blot.Results Compared with the control group,mPAP and RVHI in the experimental groups were significantly increased(P＜0.05);the expression levels of serum leptin and lung tissue OB-R were increased significantly(P＜0.05),moreover,which were positively correlated with mPAP(r=0.912,P＜0.05;r=0.861,P＜0.05).Conclusion Leptin and OB-R may play an important role in the occurrence and development of PAH induced by MCT.

Relationship Between Leptin Receptor Gene Gln223Arg Polymorphism and Metabolism Syndrome With its Impact on Left Ventricular Hypertrophy / 中国循环杂志

Objective: To explore the relationship between 1eptin receptor gene Gln223Arg polymorphism and metabolism syndrome (MS) with its impact on cardiac structure and function. Methods: Our research included 2 groups:MS group, n=167 patients with ifrst diagnosed MS without treatment in our hospital from 2005-10 to 2008-6 and Control group, n=216 healthy subjects from regular physical examination. Blood pressure, biochemical features, insulin levels and echocardiography were detected;leptin receptor Gln223Arg genotypes were measured by PCR-RFLP;the above indexes were compared between 2 groups. Results:The patients in MS group had the higher frequency of A allele than Control group. The MS occurrence rate in allele A carrier was 3.302 times higher than allele G carrier (P=0.000;95%CI 2.432-4.483). The patients in MS group already had left ventricular hypertrophy and impaired diastolic function. Compared with MS G allele carriers, the A allele carriers had the higher BMI, blood pressure, glucose, fasting glucose and insulin levels, longer waist circumference, more serious dyslipidemia and insulin resistance, left ventricular hypertrophy and impaired diastolic function. Conclusion: Leptin receptor gene Gln223Arg polymorphism is associated with the increased risk of MS occurrence and left ventricular hypertrophy.

Expression of leptin receptor and aquaporin 2 in kidneys of obesity-related hyperten-sive rats / 军事医学

Objective To observe the expression of leptin(Lep) receptor (LepR) and aquaporin 2 (AQP2) in the kidneys of obesity-related hypertensive rats ( OHR ) and to explore the mechanism of Lep resistance and water metabolic disorders in them.Methods OHR( model group) were induced by high-fat diet.Normal Wistar rats were chosen as normal control and hypertensive rats(SHR) as positive control.The serum level of triglycerides(TG), total cholesterol(TC), Lep, vasopressin ( AVP ) , angiotensinⅡ( AngⅡ) and β2-microglobulin (β2-MG ) was measured by enzyme linked immunosorbent assays ( ELISA) and renal morphology was observed by HE staining.The density of LepR and AngⅡtype 1( AT1) in the kidney was observed by immunohistochemistry.mRNA And protein expression of LepR and AQP2 in the kidney was assayed by real-time polymerase chain reaction and Western blotting.Results Compared with normal rats,the TG, TC, Lep, AVP, AngⅡand β2-MG of the model group were significantly increased (P<0.05), and protein and mRNA expression of LepR and AQP2 in the kidney were up-regulated (P<0.05).Compared with SHR group, TG, TC and Lep in serum of the model group were significantly increased (P<0.05).The concentrations of AVP,β2-MG and Lep was linearly related(R2 =0.87,R2 =0.95).Conclusion Water metabolic disorder and Lep resistance may be involved in the kidney injury of OHR, which may be one of the important pathogeneses of obesity-related hypertension.

Expression and significance of leptin receptor and phosphorylation of signal transducer and activator of transcription 3 in diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective To investigate the expression and clinical significance of leptin receptor (OBR) and phosphorylation of signal transducer and activator of transcription (p-STAT3) in patients with diffuse large B-cell lymphoma (DLBCL).Methods Immunohistochemical analysis was used to detect the expression of OBR and p-STAT3 in 80 patients with DLBCL and 10 patients with reactive lymphoid hyperplasia (RLH).Using a panel of immunohistochemical markers (CD10,bcl-6 and Mum-1),all cases of DLBCL were further divided into two groups,GCB (germinal center B-cell-like) or non-GCB.Results Immunohistochemistry revealed high expression of OBR and p-STAT3 in 45.0 ％ (36/80) and 28.8 ％ (23/80) cases of DLBCL,respectively,and minimal straining in 100.0 ％ (10/10) cases of RLH (P ＜ 0.05).Compared with GCB group (8.7 ％,2/23),non-GCB group had higher p-STAT3 high expression rate (36.8 ％,21/57) (P ＜ 0.05).There was no significant difference in the expression of OBR between these two groups.Compared with clinical stage Ⅰ-Ⅱ [46.2 ％ (18/39) and 25.6 ％ (10/39)],stage Ⅲ-Ⅳ had higher OBR and p-STAT3 high expression rate [61.9 ％ (13/21) and 38.1％ (8/21)] (P ＞ 0.05).The expression of OBR and p-STAT3 were not correlated with age,gender,extranodal infiltrations,LDH level,B-symptoms and IPI(international prognostic index)(P ＞ 0.05).The expression of OBR was positively related with that of p-STAT3 in DLBCL patients (r =0.232,P =0.039).Conclusion OBR could stimulate the JAK-STAT signaling pathway and induces the phosphorylation of STAT3.This may be involved in carcinogenesis and prognosis of DLBCL.

Dynamic fluctuation of leptin and ob-R levels of patients with trauma injury and the clinical significance / 解放军医学杂志

0.05),while the leptin level in serious injury group was higher than in all the other groups(P

Expressions of leptin receptor mRNA and neuropeptide Y mRNA in the hypothalamic arcuate nucleus of obese rat induced by high fat diet / 中华内分泌代谢杂志

The rat model of obesity was induced by high fat diet and in situ hybridization was performed with oligonucleotide probes.The results showed that expressions of leptin receptor mRNA and neuropeptide Y mRNA were significantly increased, suggesting that these increments might be related to leptin resistance.

Effects of increased complete length mRNA expression of long intracellular domain of leptin receptor on glucose oxidation metabolism in skeletal muscle cells / 中华内分泌代谢杂志

Objective To observe the effect of leptin on glucose oxidation with increased mRNA expression of complete length long intracellular domain of leptin receptor ( OBRb) in primary cultured skeletal muscle cells. Methods Skeletal muscle cells were isolated from SD sucking rat and cultured in four groups (recombinant transfection, empty plasmid transfection, non-transfection and control).The recombinant with complete length OBRb cDNA or the empty plasmid were introduced into skeletal muscle cells by clonfectin when the cultured cells were 70% conlluency, leptin and regular insulin were applied into wells and incubated for 1 h, then D-[ U-I4C]-glucose was added into wells and incubated for 2 h. The radioactivity of collected 14CO2 was assayed by scintillation. Expression level of OBRb mRNA in transfected cells was assayed by RT-PCR. Results The ratios of OBRb intraceUular domain mRNA and p-actin mRNA in cells transfected with recombinant, transiected with empty plasimd, and non-transfected were 1.22?0.10,0.41?0.08 and 0.49?0.09, respectively.The expression of OBRb intraceUular domain mRNA in cells transfected with recombinants was significantly increased as compared to the other groups of cells (P