LEP Rs7799039 Research Articles

Common Polymorphisms Linked to Obesity and Cardiovascular Disease in Europeans and Asians are Associated with Type 2 Diabetes in Mexican Mestizos.

Background and objectives: Type 2 diabetes (T2D) is a major problem of public health in Mexico. We investigated the influence of five polymorphisms, previously associated with obesity and cardiovascular disease in Europeans and Asians, on T2D in Mexican Mestizos. Materials and Methods: A total of 1358 subjects from 30 to 85 years old were genotyped for five loci: CXCL12 rs501120; CDNK2A/B rs1333049; HNF-1α rs2259816; FTO rs9939609; and LEP rs7799039. We used logistic regressions to test the effect of each locus on T2D in two case–control groups with obesity and without obesity. Also, linear regression models on glucose and glycated hemoglobin (HbA1c) were carried out on the whole sample, adjusted by age, gender, and body mass index. Results: The CXCL12 rs501120 C allele (OR = 1.96, p = 0.02), the FTO rs9939609 A allele (OR = 2.20, p = 0.04) and the LEP rs7799039 A allele (OR = 0.6, p = 0.03) were significantly associated with T2D in obesity case–control group. No significant association was found in the non-obesity case–control group. The linear regression model showed that CDNK2A/B rs1333049 C allele (β = 0.4, p = 0.03) and FTO rs9939609 A allele (β = 0.5, p = 0.03), were significantly associated with HbA1c, but no association was found among the loci with the glucose levels. Conclusions: Polymorphisms previously linked with obesity and cardiovascular events were also associated with T2D and high levels of HbA1c. Furthermore, we must point at the fact that this is the first report where polymorphisms CXCL12 rs501120 and LEP rs7799039 are associated with T2D in subjects with obesity.

Leptin gene variants and colorectal cancer risk: Sex-specific associations.

BackgroundHigh levels of serum leptin and low levels of serum adiponectin are strongly correlated with obesity, a well-established risk factor for colorectal cancer (CRC). Growing evidence suggests that dysregulation of leptin and adiponectin levels may play an etiological role in colorectal carcinogenesis. We evaluated 20 candidate variants in 4 genes previously shown to alter serum leptin and adiponectin levels for associations with obesity (BMI>30 kg/m2) and CRC risk.MethodsWe analyzed 6,246 CRC cases and 7,714 population-based controls from 11 studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations of each variant with obesity or CRC were evaluated using multivariate logistic regression models stratified by sex and adjusted for age, a study variable, and the first three principal components of genetic ancestry. Gene-specific False Discovery Rate (FDR)-adjusted p-values <0.05 denoted statistical significance.ResultsTwo variants in the leptin gene showed statistically significant associations with CRC among women: LEP rs2167270 (OR = 1.13, 95% CI: 1.06–1.21) and LEP rs4731426 (OR = 1.09, 95% CI: 1.02–1.17). These associations remained significant after adjustment for obesity, suggesting that leptin SNPs may influence CRC risk independent of obesity. We observed statistically significant interactions of the leptin variants with hormone replacement therapy (HRT) for CRC risk; these variant associations were strengthened when analyses were restricted to post-menopausal women with low estrogen exposure, as estimated by ‘never use’ of HRT and/or non-obese BMI. No variants were associated with CRC among men.ConclusionsLeptin gene variants may exhibit sex-specific associations with CRC risk. Endogenous and exogenous estrogen exposure may modify the association between these variants, leptin levels, and CRC risk.

Investigation of LEP and LEPR polymorphisms with the risk of hepatocellular carcinoma: a case-control study in Eastern Chinese Han population.

BackgroundLeptin (LEP) and LEP receptor (LEPR) polymorphisms may be associated with the development of cancer.MethodsIn this study, we selected five functional LEP and LEPR single-nucleotide polymorphisms (SNPs) and conducted a case–control study to determine the relationship of LEP and LEPR polymorphisms with hepatocellular carcinoma (HCC) risk in Eastern Chinese Han population. There were 584 HCC cases and 923 cancer-free controls included in our study. HCC patients and controls were fully matched by age and sex. SNPscan™ genotyping method was used to analyze the genotyping of LEP rs2167270 G>A, rs7799039 A>G, LEPR rs6588147 G>A, rs1137100 G>A, and rs1137101 G>A SNPs.ResultsWe found that LEP rs7799039 A>G and rs2167270 G>A polymorphisms were associated with the susceptibility of HCC in this population (LEP rs7799039 A>G: GG vs AA: adjusted odds ratio [OR]=2.03, 95% CI, 1.22–3.38, P=0.006 and GG vs AA/AG: adjusted OR=1.97, 95% CI, 1.20–3.22, P=0.007; rs2167270 G>A: AA vs GG: adjusted OR=2.03, 95% CI, 1.10–3.75, P=0.024 and AA vs GG/GA: adjusted OR=2.01, 95% CI, 1.10–3.68, P=0.023). However, LEPR rs6588147 G>A polymorphism decreased the risk of HCC (GA vs GG: adjusted OR=0.62, 95% CI, 0.45–0.86, P=0.005 and AA/GA vs GG: adjusted OR=0.64, 95% CI, 0.47–0.88, P=0.007).ConclusionThis case–control study highlights that LEP rs7799039 A>G and rs2167270 G>A polymorphisms increase the susceptibility to HCC; however, LEPR rs6588147 G>A polymorphism may be a protective factor for HCC in Eastern Chinese Han population.

Polymorphisms in Genes Involved in the Leptin-Melanocortin Pathway are Associated with Obesity-Related Cardiometabolic Alterations in a Southern Chilean Population.

Polymorphisms in genes encoding proteins of the leptin-melanocortin pathway have been associated with obesity. The involvement of these polymorphisms with changes in body mass index (BMI) and anthropometric measures could also imply a contribution to the risk of metabolic syndrome (MetS) and metabolic alterations. We evaluated the relationship of leptin-melanocortin system polymorphisms with obesity, MetS, and other metabolic alterations in Southern Chilean individuals. Two-hundred individuals were grouped as normoweight (BMI 18.0-24.9kg/m2), overweight (BMI 25.0-29.9kg/m2), and obese (BMI≥30kg/m2) or according to MetS status. Anthropometric measures (BMI, abdominal circumference, waist-to-hip ratio [WHR]) and biochemical parameters (glycemia and lipid profile) were evaluated. Polymorphisms LEP rs7799039, LEPR rs1137101, MC3R rs3746619 and rs3827103, and MC4R rs17782313 were evaluated by real-time PCR using allelic discrimination assays. LEPR rs1137101 GG genotype was related to reduced risk of obesity (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.08-0.79; p=0.018) and MetS (OR 0.36, 95% CI 0.15-0.88; p=0.024), but it was not significant after Bonferroni correction for multiple tests as compared to the AA genotype (p>0.01). Moreover, LEPR rs1137101 allele G (AG+GG) was related to lower BMI and WHR (p<0.01). Further multiple linear regression analysis demonstrated that this genotype was also responsible for reduced BMI in 2.44kg/m2 and WHR in 0.033 units. MC4R rs17782313 allele C (TC+CC) was slightly associated with diminished risk of MetS (OR 0.48, 95% CI 0.23-0.98; p=0.040) and reduced BMI values in 1.95kg/m2 (p<0.05). Regarding lipid profile, LEPR rs1137101 allele G carriers had lower triglycerides and very-low-density lipoprotein (VLDL) cholesterol, whereas individuals carrying the MC4R rs17782313 allele C had higher high-density lipoprotein (HDL) cholesterol (p<0.01). LEP rs7799039 allele A (GA+AA) was slightly associated with reduced total and low-density lipoprotein (LDL) cholesterol (p<0.05). These results suggest that polymorphisms at LEP, LEPR, and MC4R may be useful biomarkers of obesity-related cardiometabolic alterations in our population.

Study of the association between polymorphism of persistent obesity, human leptin gene/leptin receptor gene and molecular subtypes of breast cancer

Objectives: To explore the association between the polymorphism of persistent obesity and genetic variations in the LEP (human leptin gene, LEP) and LEPR (leptin receptor gene, LEPR) genes and different molecular subtypes of breast cancer. Methods: All 703 female patients of breast cancer diagnosed by histopathology in the Sichuan Cancer Hospital or the West China Hospital, excluding patients with metastatic breast cancer or mental disease, were selected as cases from April 2014 to May 2015. At the same time, 805 healthy women received physical examination in medical examination center of Sichuan People Hospital or Shuangliu maternal and child health care hospital, excluding those with therioma, breast disease, and mental disease, were enrolled in control group. A uniform questionnaire was used to collect general information including demographic characteristic, reproductive history height, weight, and so on. And the obesity status in recent 10 years was judged. Time of Flight Mass Spectrometer was used to determine the genotypes of LEP rs7799039, LEPR rs1137100 and LEPR rs1137101, while the multinomial logistic regression analysis was conducted to estimate the effect of risk factors related to breast cancer in different molecular subtypes; and then, the association between polymorphism of persistent obesity, the LEP, LEPR genes and breast cancer of different molecular subtypes was analyzed by binary logistic regression models. Results: The average age of controls was (48.98±8.83) years old, while the age of cases of TNBC, Luminal A, Luminal B, and HER-2+ were (51.43±11.33), (49.94±10.10), (49.73±9.38), (50.50±9.04) years old, respectively. The frequency of genotype LEP rs7799039, LEPR rs1137100 and LEPR rs1137101 in control group was separately 74.8%(1 157/1 546), 83.6%(1 339/1 602) and 88.4%(1 416/1 602); while 77.6% (1 074/1 384), 82.4% (1 155/1 402) and 87.9% (1 232/1 402) respectively in case group. Compared with non-persistent obesity subjects, the persistent obesity ones showed an increased risk in TNBC (OR=3.58, 95%CI: 1.90-6.72), Luminal A (OR=2.65, 95%CI: 1.35-5.21) and Luminal B (OR=1.90, 95%CI: 1.26-2.89) breast cancer. LEP rs7799039-AA was relevant with the upward risk of Luminal B independently (OR=1.30, 95%CI: 1.00-1.69). Besides, persistent obesity was found to have a combined effect on Luminal B (β=3.34, 95% CI: 1.00-11.12) with LEPR rs1137101-GG. Conclusion: Persistent obesity could increase the potential risk of TNBC, Luminal A and Luminal B breast cancer. Women who were suffered from persistent obesity with a genotype of LEPR rs1137101-GG were more susceptible to Luminal B breast cancer.

Genetic polymorphisms of IL-23R (rs7517847) and LEP (rs7799039) among Egyptian patients with hepatocellular carcinoma

Background: Genetic polymorphisms of IL-23 R (rs7517847) and LEP (rs7799039) have been stated to be associated with various types of human cancers. The purpose of this work is to test the association of these genetic polymorphisms with hepatocellular carcinoma (HCC) among Egyptian patients.Subjects and methods: This study involved 150 unrelated Egyptian HCC patients in addition to 100 healthy controls from the same locality. DNA was genotyped for these genetic polymorphisms using the PCR-RFLP technique.Results: The frequency of the IL-23 R (rs7517847) G and LEP (rs7799039) G alleles were significantly higher among HCC patients compared to controls (p = .004 and .02). However, HCC patients with the IL-23 R GG and LEP GG genotypes showed no significant difference compared to others regarding their clinical and laboratory markers.Conclusions: IL-23 R (rs7517847) and LEP (rs7799039) polymorphisms were associated with an increased risk but not affecting the clinical presentation of HCC among Egyptian patients.

Adiponectin and leptin gene polymorphisms in women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the glucose intolerance occurring during pregnancy. The prevalence of GDM is increased in obese women. Leptin and adiponectin are adipokines that play an important role in the regulation of insulin secretion and glucose and lipid metabolism. The aim of this study was to examine the association between adiponectin and leptin gene polymorphisms and the development of GDM. This case-control study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test (OGTT) at 24-28weeks' gestation. To discriminate the ADIPOQ rs266729, rs1501299 and LEP rs2167270 alleles, TaqMan® Pre-Designed SNP Genotyping Assays were used. There was a statistically significant association between the ADIPOQ rs266729 gene polymorphism and GDM. Among women with GDM, a higher prevalence of the G allele was observed (GG and CG genotypes). Multivariate logistic regression analysis, taking into account age, BMI before pregnancy, past pregnancies and the ADIPOQ rs266729 gene polymorphism, revealed that the presence of a G allele is an independent risk factor for GDM. Moreover, there was the association between the LEP rs2167270 polymorphism and the requirement for daily insulin, which was significantly higher in women with the A allele (AA and GA genotypes). The results of our study suggest an association between adiponectin gene rs266729 as well as leptin gene rs2167270 polymorphisms and GDM.

Association between gene polymorphisms and obesity and physical fitness in Korean children.

Obesity is affected by genetic factors and environmental influences. This research was undertaken to identify single nucleotide polymorphisms (SNPs) related to obesity and physical fitness and then to analyse and compare interactions between physical fitness and obesity-associated genotypes. To investigate relationships between physical fitness and major SNPs previously reported to be related to obesity, 68 SNPs in 32 genes were genotyped in 71 Korean children. Tests were conducted to evaluate five elements of physical fitness (speed, aerobic endurance, muscular endurance, muscular strength, and flexibility). The results obtained showed significant (P<0.02) differences in physical fitness scores for the following genotypes: CNR1 (rs1049353; GG), LEP (rs7799039; AA+AG), HHEX (rs1111875; TT), GC (rs16847015; TG+GG), LRP5 (rs4988300; GG+GT), NPY2R (rs2880415; CT+CC), PPY (rs231472; GG), UCP2 (rs660339; CT+TT), CDKN2B (rs10811661; AA+AG), and ADIPOQ (rs266729; CG+GG). Ten physical fitness-related genotypes were newly identified during the present study. This study suggests that classification of genotypes by physical fitness level could be used as an index for predicting the risk of obesity and for selecting individuals for intervention programmes. Furthermore, the study shows that even children participating in the same physical fitness improvement programme can exhibit different genotype dependencies.

Genetic polymorphisms in leptin, adiponectin and their receptors affect risk and aggressiveness of prostate cancer: evidence from a meta-analysis and pooled-review.

Leptin and adiponectin signaling was associated with development and progression of various cancers. The present study aimed to clarify the role of genetic variants in leptin, adiponectin and their receptors in prostate cancer. After comprehensive search and manuscript scanning, a total of 49 genetic variants were enrolled and examined for their relations to cancer risk and aggressiveness. In the meta-analysis, LEP rs7799039 (allele contrast: OR 1.133, 95%CI 1.024-1.254), ADIPOQ rs2241766 (allele contrast: OR 1.201, 95%CI 1.015-1.422) and ADIPOR1 rs10920531 (allele contrast: OR 1.184, 95%CI 1.075-1.305) variants were identified to be correlated with increased risk of prostate cancer. On the contrary, LEPR rs1137101 (allele contrast: OR 0.843, 95%CI 0.730-0.973) and ADIPOR1 rs2232853 (allele contrast: OR 0.638, 95%CI 0.535-0.760) variants were associated with decreased risk of prostate cancer. From the pooled-review, we additionally recognized eight variants associated with cancer risk and another eight variants associated with cancer aggressiveness, respectively. These observations indicated important roles of leptin, adiponectin and their receptors in the development and progression of prostate cancer. The identified polymorphisms might assist in developing better risk-assessment tools, as well as generating novel targeted therapies, especially for obese cancer patients with impaired leptin and adiponectin signaling.

Association of ADIPOQ, LEP, and FTO gene polymorphisms with large for gestational age infants.

The main objective of this study was to evaluate the effect of the ADIPOQ rs2241766, LEP rs7799039, and FTO rs9939609 polymorphisms on the birth weight status of Brazilian infants. This cross-sectional study was conducted in southern Brazil. Large for gestational age (LGA) newborns (n = 105), and the same number of small for gestational age/adequate for gestational age newborns, were included. Genotyping of the rs2241766, rs7799039, and rs9939609 polymorphisms was done by PCR-RFLP analysis. Logistic regression was used to investigate the association between LGA newborns and the presence of the polymorphisms. Infants carrying the GG genotype of the rs7799039 polymorphism were 2.12 times more likely to be born LGA than those carrying the GA + AA genotypes (95% CI: 1.17-3.83). These results did not change substantially after adjusting for potential confounding variables (OR = 1.98; 95% CI 1.05-3.73) and adjustment for the three polymorphisms (OR = 1.98; 95% CI 1.05-3.74). Regarding the ADIPOQ polymorphism, newborns carrying the TG or GG genotype were 1.88 times more likely to be born LGA than those carrying the TT genotype, although this difference was not statistically significant (p = 0.082). No association was found between the FTO gene polymorphism and newborn weight status. This study showed that the GG genotype of the LEP polymorphism rs7799039 is a risk factor for LGA infants. The exact role and mechanism of action of the GG genotype of this polymorphism in weight status control remain to be elucidated, and more studies are needed.

ADIPOQ -11377C>G Polymorphism Increases the Risk of Adipokine Abnormalities and Child Obesity Regardless of Dietary Intake.

The aim of the present study was to verify whether selected functional single nucleotide polymorphisms in LEP, LEPR, and ADIPOQ loci are associated with the development of obesity and serum levels of the respective adipokines in prepubertal white children with obesity. Frequencies of -2548G>A LEP (rs7799039), Q223R (rs1137101) and K656N (rs8129183) LEPR, and -11377C>G (rs266729) and -11426A>G (rs16861194) ADIPOQ polymorphisms were analyzed by restriction fragment length polymorphism in 101 obese (standard deviation score [SDS]-body mass index [BMI] >2) and 67 normal-weight (SDS-BMI <- 1 + 1 >) children. Serum adipokine concentrations were measured using the enzyme-linked immunosorbent assay method. The GC/GG genotypes of -11377C>G ADIPOQ polymorphism were associated with a higher risk of obesity (P = 0.022, odds ratio 2.08 [95% confidence interval 1.11-3.90]). Individuals carrying the GG genotype had a higher leptin/total adiponectin ratio by 25% than CC homozygotes (P trend = 0.05). In the multivariate linear regression model, we found differences among particular genotypes of this polymorphism in concentrations of high molecular weight (HMW) adiponectin (P trend = 0.043) and HMW/total adiponectin ratio (P trend = 0.048), with the lowest values in GG homozygotes. Positive correlations between SDS-BMI and dietary reference intake percentage were observed in individuals homozygous for allele C (r = 0.403, P = 0.01) and CG heterozygotes (r = 0.428, P = 0.004). No significant correlations between both parameters were found in the GG homozygotes. Among the analyzed polymorphisms, only -11377C>G ADIPOQ single nucleotide polymorphism was associated with obesity during the prepubertal period. Adipokine abnormalities coexisting with the lack of relations between SDS-BMI and dietary intake may predict a higher risk of future obesity-related disorders in obese children carrying the GG genotype than in those with other genotypes.

Adiponectin and leptin gene polymorphisms in patients with post-transplant diabetes mellitus.

Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after organ transplantation and may be associated with the use of calcineurin inhibitors (tacrolimus and cyclosporine). Leptin and adiponectin are adipokines and play an important role in the regulation of insulin secretion as well as glucose and lipid metabolism. The aim of this study was to examine the association between adiponectin and leptin gene polymorphisms and development of PTDM. The study included 323 patients who received kidney transplants and were treated with calcineurin inhibitors (tacrolimus or cyclosporine). The association between adiponectin and leptin gene polymorphisms and PTDM was studied in three models of Cox regression analysis--additive, dominant and recessive. In these three models, the LEP rs2167270 gene polymorphism was statistically significantly associated with increased risk of PTDM. The association between the LEP rs2167270 polymorphism and PTDM was confirmed by multivariate regression analysis. The results of our study suggest an association between the leptin rs2167270 gene A allele and PTDM. Original submitted 27 February 2015; Revision submitted 22 May 2015.

Gene polymorphisms and increased DNA damage in morbidly obese women

Obesity is characterized by increased adipose tissue mass resulting from a chronic imbalance between energy intake and expenditure. Furthermore, there is a clearly defined relationship among fat mass expansion, chronic low-grade systemic inflammation and reactive oxygen species (ROS) generation; leading to ROS-related pathological events. In the past years, genome-wide association studies have generated convincing evidence associating genetic variation at multiple regions of the genome with traits that reflect obesity. Therefore, the present study aimed to evaluate the relationships among the gene polymorphisms ghrelin (GHRL–rs26802), ghrelin receptor (GHSR–rs572169), leptin (LEP–rs7799039), leptin receptor (LEPR–rs1137101) and fat mass and obesity-associated (FTO–rs9939609) and obesity. The relationships among these gene variants and the amount of DNA damage were also investigated. Three hundred Caucasian morbidly obese and 300 eutrophic (controls) women were recruited. In summary, the results demonstrated that the frequencies of the GHRL, GHSR, LEP and LEPR polymorphisms were not different between Brazilian white morbidly obese and eutrophic women. Exceptions were the AA-FTO genotype and allele A, which were significantly more frequent in obese women than in the controls (0.23% vs. 0.10%; 0.46 vs. 0.36, respectively), and the TT-FTO genotype and the T allele, which were less frequent in morbidly obese women (p<0.01). Furthermore, significant differences in the amount of genetic lesions associated with FTO variants were observed only in obese women. In conclusion, this study demonstrated that the analyzed SNPs were not closely associated with morbid obesity, suggesting they are not the major contributors to obesity. Therefore, our data indicated that these gene variants are not good biomarkers for predicting risk susceptibility for obesity, whereas ROS generated by the inflammatory status might be one of the causes of DNA damage in obese women, favoring genetically related diseases as obesity comorbidities.

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

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.

Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia

Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment.

Leptin and leptin receptor genotypes and colon cancer: Gene–gene and gene–lifestyle interactions

Leptin may play an important role in colorectal cancer because of its role in energy balance, insulin and inflammation. We evaluated the LEP rs2167270 (19 G > A) and rs7799039 (-2548 G > A) polymorphisms and the leptin receptor, LEPR rs6588147 (located in intron 2), polymorphism with risk of developing colon cancer in a study of 1,567 cases and 1,965 controls. We evaluated the effects of the polymorphisms with body mass index (BMI), recent use of aspirin/NSAIDs and genetic variations in genes related to insulin signaling pathways including insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), and insulin-related substrates 1 and 2 (IRS1, IRS2) and the vitamin D receptor (VDR). We observed a slight reduction in colon cancer risk with the AA LEP rs2167270 genotype (OR 0.79 95% CI 0.64, 0.98) and although not reaching statistical significance, with the combined GG LEP rs2167270 and GG LEPR rs6588147 (OR 0.70, 95% CI 0.49, 1.02) genotypes. BMI did not interact with any of these polymorphisms to alter colon cancer risk. However, recent aspirin/NSAID use significantly interacted with both LEP polymorphisms. Likewise, variants of IGF1 and IRS2 interacted with the LEP rs2167270 polymorphism. VDR polymorphisms interacted with all LEP and LEPR polymorphisms. These data support an association between LEP and colon cancer. They also suggest that the mechanisms linking leptin to colon cancer may be independent of energy balance.