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Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer.

ABSTRACT: Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98?ng/mL) than those with AG genotype (10.07 ± 0.60?ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59?ng/mL) than the subjects with GG genotype (9.52 ± 0.79?ng/mL; P < 0.05). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; P = 0.0183; 95% CI, 1.516-90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; P = 0.027; 95% CI, 1.161-12.092 and OR, 5.437; P = 0.013; 95% CI, 1.426-20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness.

SUBMITTER: Marcello MA

PROVIDER: S-EPMC4355553 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer.

Marcello Marjory Alana MA Calixto Antonio Ramos AR de Almeida Jacqueline Fatima Martins JF Martins Mariana Bonjiorno MB Cunha Lucas Leite LL Cavalari Camila Ayume Amano CA Etchebehere Elba C S EC da Assumpção Ligia Vera Montalli LV Geloneze Bruno B Carvalho Andre Lopes AL Ward Laura Sterian LS

International journal of endocrinology 20150225

Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0. ...[more]

PMID: 25810718

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Project description:Obesity is associated with breast cancer in post-menopausal women, and breast density is a marker of breast cancer risk. Leptin is produced by the adipose tissue, acts through receptors that are polymorphic in nature, and is considered a cancer growth factor. The relationship between body mass index, leptin, leptin receptors and breast density is not well studied. A cross-sectional analysis in 392 post-menopausal healthy women was conducted; participants provided permission to obtain copies of their most recent screening mammogram. Non-fasting plasma leptin levels were determined using a commercially available leptin ELISA kit. Analysis of the Q223R genotypes of the LEPR gene were performed by PCR followed by restriction fragment length polymorphism analysis using DNA extracted from buffy coat samples. A statistically significant positive relationship was observed between leptin levels and body mass index (p<0.0001); leptin was significantly positively associated with mammography total breast area and non-dense breast area (p<0.0001), while it was inversely associated with percent breast density (p<0.0001). Leptin levels varied across the LEPR Q223R polymorphism, and were higher in women homozygous for the AA variant. Percent breast density decreased across the LEPR Q223R genotype, with lower percent density in women with the AA genotype. When dense area was considered according to quartiles of leptin and stratified by LEPR Q223R, a significant inverse trend between leptin levels and dense breast area was observed only among women with the G/G genotype (p-trend<0.001). After adjustment for possible confounders, leptin levels were significantly inversely associated with percent breast density (p=0.01). A significant interaction between body mass index and leptin levels on percent breast density was observed (p=0.03). These findings suggest that the association between leptin and breast density may vary by LEPR Q223R genotype, and that body mass index and leptin may act in an interactive way in determining breast density.

Project description:BACKGROUND:Metabolic syndrome is a cluster of metabolic risk factors including dyslipidemia, impaired glucose tolerance, hypertension and central obesity. BDNF (Brain-derived neurotrophic factor) and leptin have been implied in the energy homeostasis. The purposes of this study were to examine concentrations of leptin, BDNF and biochemical parameters in metabolic-syndrome subjects and healthy controls, and also to search for associations of leptin gene (LEP) G2548A, leptin receptor gene (LEPR) Gln223Arg, and BDNF gene (BDNF) Val66Met polymorphisms with leptin levels, BDNF levels and metabolic syndrome among Thais. METHODS:The case-controlled design was performed using 322 Thai volunteers (160 metabolic-syndrome subjects; 162 controls) during the health screening program. Metabolic syndrome was assessed by using the modified National Cholesterol Education Program, Adult Treatment Panel III criteria. The levels of leptin, BDNF, insulin, glucose and lipids were measured in samples. Genotyping of LEP G2548A, LEPR Gln223Arg and BDNF Val66Met was carried out using polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS:Serum leptin levels were significantly higher in the metabolic-syndrome group than the control group (p < 0.01), but the BDNF difference between them was not significant. Significant associations of LEPR Gln223Arg polymorphism were found with leptin and glucose levels (p < 0.05), after adjusting for potential covariates. This LEPR polymorphism in the metabolic-syndrome group was also significantly more frequent than in the control group (p < 0.05). However, other gene polymorphisms, LEP G2548A and BDNF Val66Met, showed no significant relationship with leptin levels, BDNF levels or metabolic syndrome. CONCLUSION:These findings suggest leptin levels are linked with metabolic syndrome. LEPR Gln223Arg polymorphism impacted leptin concentrations, and this gene polymorphism may influence susceptibility to metabolic syndrome among Thais.

Project description:BackgroundAutoimmune thyroid disease (AITD) comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD.MethodsPolymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case-control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays.ResultsA significant association was found between the allele A in TNFA-308 G/A and Hashimoto's thyroiditis, both in the dominant (OR?=?1.82, CI?=?1.37-2.43, p-value?=?4.4×10(-5)) and log-additive (OR?=?1.64, CI?=?1.28-2.10, p-value?=?8.2×10(-5)) models. The allele C in IL6-174 G/C is also associated with Hashimoto's thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR?=?1.28, CI?=?1.06-1.54, p-value?=?8.9×10(-3)). The group with Graves' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR?=?1.85, CI?=?1.19-2.87, p-value?=?7.0×10(-3)) and log-additive (OR?=?1.69, CI?=?1.17-2.44, p-value?=?6.6×10(-3)) models. The risk for Hashimoto's thyroiditis and Graves' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59).ConclusionsThis study reports significant associations of genetic variants in TNFA and IL6 with the risk for AITD, highlighting the relevance of polymorphisms in inflammation-related genes in the etiopathogenesis of AITD.

Project description:BackgroundObesity has become the main health issue in developed countries as it impacts life expectancy and increases mortality of cerebrovascular or cardiovascular diseases. The leptin is one of the adipokines which presents in the serum in proportion to the amount of adipose tissue and is translated from LEP gene. It involves in energy homeostasis, lipid and glucose metabolisms, modulation of immune systems, and thermogenesis. Many previous studies have revealed controversial results between LEP polymorphisms and leptin levels in different ages and ethnicities. Herein, we investigated the impacts of LEP polymorphism against leptin levels in Taiwanese subjects.MethodsIn 599 Taiwanese subjects, excluding clinically overt systemic disease, age below 18 years old, and C-reactive protein (CRP) level of above 10 mg/L, few of LEP polymorphisms were genotyped with TaqMan SNP genotyping assays, were further analyzed for association with leptin level in univariate and multivariate linear regression analyses with Bonferroni correction for multiple tests in stratified groups. The univariate and stepwise multivariate linear regression analyses were performed to determine the coefficient of determinant of LEP polymorphisms over leptin level.ResultsSignificant associations were found between LEP polymorphisms and leptin levels in obese women. Circulating leptin level was positively correlated with inflammatory, insulin resistance markers, and visceral obesity markers in all subjects. Furthermore, stratified and interaction analyses revealed that LEP polymorphisms, rs7799039 and rs2167270, were significantly associated with leptin levels in obese women-8%-10% of which could be explained by LEP polymorphisms.ConclusionThe LEP polymorphisms are independently associated with leptin levels in Taiwanese obese women. Further, the genetic determinants for leptin levels may be different between obese and nonobese, and in different sex individuals. The obesity status and female sex may exert modification effect on transcription of LEP, particularly in obese women.

Dataset Information

Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer.

Publications

Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer.

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