Leptin Receptor Rs1137101 Research Articles

LEP rs7799039 and LEPR rs1137101 gene variants are not associated with clinical features in patients with metabolic syndrome in the Turkish population.

Genetic predisposition plays a role in the etiology of metabolic syndrome (MetS), an important health problem worldwide. Leptin (LEP), produced by adipose tissue, plays a crucial role in the development of MetS. In this study, we evaluated the effects of LEP and LEP receptor (LEPR) variants on clinical findings and risk of developing MetS in the Turkish population. A total of 320 patients were included in the study, of whom 150 were patients with MetS and 170 were healthy controls. DNA was extracted from blood samples. LEP rs7799039 and LEPR rs1137101 variants were genotyped using the polymerase chain reaction-based restriction fragment length polymorphism method. The genotype distributions of these variants and clinical and laboratory findings were compared. The LEP rs7799039 GA and AA genotypes and A allele frequencies were higher in participants with MetS than in the control group. For LEP rs7799039, the genotype AA-GA was higher in males, and the GG genotype was higher in females. On analyzing the clinical outcomes associated with these variants, it was observed that individuals possessing LEP rs7799039 GA and AA genotypes displayed elevated levels of triglycerides. In addition, those with the AG-GG genotype of LEPR rs1137101 had lower mean hemoglobin levels. Our results showed that the LEP rs7799039 and LEPR rs1137101 variants may be associated with both the risk of MetS development and clinical findings. Among the various contributors to MetS, a genetic predisposition is commonly recognized as the primary cause.

Circulating leptin level in osteoarthritis and associations between leptin receptor polymorphisms and disease susceptibility: A meta-analysis.

This study aimed to systemically review the evidence on the relationship between the circulating leptin levels and osteoarthritis (OA), and the association between leptin and leptin receptor (LEPR) polymorphisms and OA susceptibility. To find relevant papers (up to February 2023) examining the association between circulating leptin levels, LEPR polymorphisms, and OA, the PUBMED, EMBASE, and Cochrane databases were searched. We performed a meta-analysis to examine the levels of synovial and serum/plasma leptin in OA patients compared with healthy controls, as well as the relationship between OA and LEPR polymorphisms. Data from 15 investigations, totaling 2197 patients with OA and 2546 controls, were included in the meta-analysis. There were statistically significant differences in the levels of circulating leptin between the OA and control groups (standardized mean difference [SMD] 2.178, 95% confidence interval [CI] 1.208-3.139, P = 0.001). Leptin levels were also substantially greater in European, Asian, and Arab groups among OA patients. After adjusting for age, sex, and/or body mass index, the leptin levels of patients with OA were significantly higher. Similarly, regardless of sample size (n < 100 and n ≥ 100) or year of publication, leptin levels were considerably higher in the OA group. In addition, the synovial leptin level was greater in the OA group than in the control group (SMD 0.783; 95% CI 0.247-1.319, P = 0.004). In the LEPR rs1137101 polymorphism, the OA and AA genotypes were significantly associated (odds ratio 0.282, 95% CI 0.126-0.629, P = 0.002), according to the meta-analysis. Ethnic stratification revealed an association between OA and the LEPR rs1137101 AA genotype in Asian and Arab populations. The results of this meta-analysis indicate that patients with OA had considerably greater levels of circulating leptin than did control individuals. In addition, synovial leptin levels were greater in OA patients than in healthy individuals, and the LEPR rs1137101 polymorphism was linked to an increased risk of developing OA. These results imply that leptin participates in the onset and progression of OA.

Influence of the polymorphisms leptin rs7799039, leptin receptor rs1137101, biochemical, and somatometric parameters as risk factors for developing type 2 diabetes in Mexican patients

Introduction. The role of leptin in humans is an essential factor in the pathophysiology of obesity and type 2 diabetes (T2D); and it is also related to their comorbidities. The objective of this study was to determine the influence together of rs7799039 (-2548G &gt; A) LEP and rs1137101 (223Gln &gt; Arg) LEPR polymorphisms, as well as biochemical and somatometric parameters, as risk factors for T2D. Material and Methods. A cross-sectional case-control study with a control group and a case group. Both groups were matched by age, sex, and body mass index. The genes were amplified by conventional PCR and were genotyped by restriction fragment length polymorphism (RFLP) analysis. Polymorphims were validated using real-time PCRand TaqMan® probes in triplicate. Sample size was determined using an equation for cases and controls. Genomic DNA was isolated from leukocytes of peripheral blood samples using the DTAB/CTAB method and gene amplification was performed by conventional PCR. The presence of the polymorphisms was validated using real-time PCR and Applied Biosystems® TaqMan® probes C_3001671_10 for leptin and C_8722581_10 for leptin receptorpolymorphisms. Results. The polymorphism LEP rs7799039 in genotypes G/A, and A/A, was associated with T2D [OR = 2.23 C = 1.13 to 4.37 and OR = 2.62 CI = 1.27 to 5.40, respectively]. Additionally, polymorphism rs1137101 in genotypes A/G and G/G was associated with T2D (OR = 0.35, IC = 0.17 to 0.72 and OR = 4.7, CI = 2.29 to 9.62, respectively). Analyzed together, the combined genotypes GA-2548/GG223 (OR = 7.61 CI = 2.02 to 28.67) and AA-2548/GG223 (OR = 3.53 CI = 1.14 to 10.92) were found to be strongly associated with T2D. Remarkably, the combined genotype GG-2548/AA223 and AA-2548/AA223 tended to be a protective factor against T2D (OR = 0.28, CI=0.08 to 0.47 and OR = 0.26, CI = 0.08 to 0.81). Conclusions. LEP and LEPR polymorphisms are associated with T2D in this population. Notably, the combined genotypes GG-2548/AA223 and AA-2548/AA223 are factors associated with a reduced risk of T2D, while the GA-2548/GG223 and AA-2548/GG223 genotypes combined conform a risk factor for T2D. Our findings warrant future cohort studies.

Association of leptin and leptin receptor genes variants and pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population

BackgroundThe aim of our study was to investigate the association of leptin (LEP) gene (rs11761556, rs12706832, rs2167270), leptin receptor (LEPR) gene (rs1137100, rs1137101, rs1805096) variants and pulmonary tuberculosis (PTB) susceptibility, as well as their several clinical manifestations, in a Chinese population. MethodsThis study included a cohort of 489 PTB patients and 489 healthy controls, and six SNPs were genotyped by improved multiple ligase detection reaction (iMLDR). ResultsWe found that there were no significant differences regarding the allele and genotype frequencies of LEP rs11761556, rs12706832, rs2167270, LEPR rs1137100, rs1137101, rs1805096 between PTB patients and healthy controls (all P > 0.05), as well as the results of the dominant model and recessive model (all P > 0.05). In the LEP gene, the rs11761556 AA genotype frequency was significantly associated with the development of fever and pulmonary infection in PTB patients (P = 0.035, P = 0.049). In addition, the relation between main haplotypes and PTB patients was also analyzed, but only haplotype CAG in LEP was significantly associated with PTB susceptibility (P = 0.012). ConclusionsLEP and LEPR heritable variation were not contribute to the pathogenesis of PTB in Chinese. While rs11761556 variant might associate with several clinical features of PTB.

Association of PON1, LEP and LEPR Polymorphisms with Susceptibility to Breast Cancer: A Meta-Analysis.

Objective:Breast cancer is the most common cancer in American women, except for skin cancers. In this meta-analysis, the associations of polymorphisms within paraoxonase 1 (PON1), leptin (LEP) and leptin receptor (LEPR) genes with susceptibility to breast cancer were comprehensively evaluated. Methods:A universal search in PubMed, Scopus, CNKI, SID, Web of Knowledge and Google Scholar was performed to identify relevant studies up to 01 May, 2021. The strength of the associations was estimated by Odds ratios (ORs) with 95% confidence intervals (95% CIs). Results:A total of 39 case-control studies including 7 studies with 2005 cases and 2748 controls were on PON1 rs662, 6 studies with 2,031 cases and 1,973 controls on PON1 rs854560, 12 studies with 3,444 cases and 3,583 controls on LEP rs7799039, and 14 studies with 5,330 cases and 6,188 controls on LEPR rs1137101 were selected. Pooled data showed that PON1 rs662 and rs854560 polymorphisms were associated with risk of breast cancer in overall population, but not LEP rs7799039 and LEPR rs1137101. Conclusions:Our pooled data revealed that the PON1 rs662 and rs854560 polymorphisms were significantly associated with an increased risk of breast cancer in the overall population. However, LEP rs7799039 and LEPR rs1137101 polymorphisms were not associated.

Association study of rs7799039, rs1137101 and rs8192678 gene variants with disease susceptibility/severity and corresponding LEP, LEPR and PGC1A gene expression in multiple sclerosis

Leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1A) are involved in the pathogenesis of multiple sclerosis (MS) by affecting the inflammatory response and reactive oxygen species production. LEP rs7799039 and LEPR rs1137101 genetic variants modify the serum LEP levels and PGC1A rs8192678 alters the PGC1A activity. The study objective was to explore the associations of these variants with susceptibility to MS, disease course/clinical parameters and also with peripheral blood mononuclear cell expression of the target genes and plasma LEP concentrations, in the study subjects. The study groups included 528 patients with MS and 429 controls. TaqMan® assays were used for genotyping and gene expression quantification. The Chi-square, parametric and nonparametric tests and simple/multiple logistic regression were performed for the statistical analysis of data. A multiple logistic regression model including all three investigated variants, applied to patients (RRMS+SPMS) and controls, showed that PGC1A rs8192678 minor allele had an increased risk for the occurrence of disease, with OR (95%CI)=1,32 (1,01-1,73), P=0,04. Between-effect of gender and LEPR variant on the multiple sclerosis severity score (MSSS) was identified (P=0,005). In male patients (relapsing-remitting and secondary progressive), LEPR minor allele carriers had increased MSSS (GG+AG vs AA, median (minimum-maximum)=5,38 (0,64-9,88) vs 4,27 (0,78-9,63); P=0,01, Padj=0,03). In relapsing-remitting patients LEP rs7799039 affected the LEP gene expression (P=0,006; Padj=0,04). The current findings implicate an impact of investigated genetic variants on the pathogenesis of MS.

Combined donor-recipient genotypes of leptin receptor and adiponectin gene polymorphisms affect the incidence of complications after renal transplantation

BackgroundWe aimed to examine whether combined donor/recipient variants in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes may affect outcomes in renal transplantation. MethodsA total of 233 donors and their corresponding 307 recipients were genotyped for LEPR rs1805094, rs1137100 and rs1137101, and ADIPOQ rs1501299 and rs224176. Combined donor/recipient genetic scores were created to investigate associations with delayed graft function (DGF), graft loss and estimated glomerular filtration rate (eGFR). ResultsRecipients whose donors carried variant alleles of LEPR rs1137100 and rs1137101 had lower risk of DGF [OR = 0.48 (0.24–0.97), p = 0.040] and [OR = 0.47 (0.23–0.95), p = 0.035], respectively. In addition, rs1137101 also showed an inverse association with lower incidence of graft loss [OR = 0.44 (0.31–0.97), p = 0.040]. The analysis of genetic scores of donor/recipients showed that again rs1137101 was inversely associated with both outcomes: OR = 0.46 (0.23–0.92), p = 0.029 and OR = 0.45 (0.11–0.81), p = 0.009, respectively. With regard to graft function, the T-allele of ADIPOQ rs1501299 in the donor was related to higher eGFR values (75.26 ± 29.01 vs. 67.34 ± 25.39 ml/min for wild-type grafts, p = 0.012). Higher combined genetic scores in this same polymorphism were also associated with better function (78.33 ± 31.87 vs. 68.25 ± 24.32 ml/min, p = 0.018). Finally, eGFR values were similar between paired kidneys but they were different when comparing grafts with or without the rs1501299 T-variant (77.87 ± 26.50 vs. 69.27 ± 26.73 ml/min, p = 0.016). ConclusionsOur study has shown for the first time to our knowledge that variants in LEPR and ADIPOQ genes of the donors and/or their combination with those in the recipients may affect the outcome of renal transplantation.

Leptin rs7799039 polymorphism is associated with multiple sclerosis risk in Kuwait

BackgroundLeptin association with Multiple sclerosis (MS) pathogenesis and MS related clinical characteristics is inconsistent. Here, we investigated whether two common variants in leptin (LEP) and leptin receptor (LEPR) genes influence MS risk and leptin levels in MS patients. MethodsIn a case-control study including 169 MS patients and 100 controls we examined the association of leptin in MS. Blood samples were used for DNA extraction and plasma retrieval. Taqman genotyping assays were used for LEP rs7799039 and LEPR rs1137101 genotyping, and enzyme-linked immunosorbent assay for plasma leptin level. ResultsLeptin levels were significantly lower in MS patients compared to controls (β = 0.157, 95%CI: 0.033–0.26, p = 0.012). LEP rs7799039AA associated with MS risk (OR: 2.52; 95%CI: 1.35–4.67, p = 0.003). None of the assessed markers associated with MS disability, severity or response to treatment. ConclusionLEP rs7799039AA is a risk factor for MS in our Kuwaiti population, and leptin levels are lower in MS patients compared to healthy controls. Our findings suggest future studies must consider all factors influencing leptin levels to resolve its controversial involvement in MS pathogenesis or progression.

Associations of Leptin Receptor and Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms with Polycystic Ovary Syndrome: A Meta-Analysis

Background: Previous studies on associations of leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma (PPARG) polymorphisms with polycystic ovary syndrome (PCOS) yielded conflicting results. Objectives: In this meta-analysis, we aimed to better analyze the relationship between LEPR/PPARG polymorphisms and PCOS in a larger pooled population. Methods: We performed a systematic search of PubMed, Web of Science, Embase and CNKI. We calculated pooled ORs and 95% CIs to estimate associations between LEPR/PPARG polymorphisms and PCOS. Results: Totally, 33 eligible studies were included. A significant association with susceptibility to PCOS was observed for LEPR rs1137101 polymorphism under recessive genetic model (p = 0.002, OR 1.88, 95% CI 1.26–2.78, I² = 42%) and for PPARG rs1801282 polymorphism under dominant (p = 0.007, OR 1.20, 95% CI 1.05–1.36, I² = 49%), overdominant (p = 0.02, OR 0.85, 95% CI 0.74–0.97, I² = 48%), and allele (p = 0.006, OR 1.18, 95% CI 1.05–1.33, I² = 47%) genetic models in overall population. Further subgroup analyses by ethnicity revealed that LEPR rs1137101 and PPARG rs3856806 polymorphisms were both significantly associated with susceptibility to PCOS in Asians. No any positive results were detected in overall and subgroup analyses. Conclusions: Our meta-analysis suggested that LEPR rs1137101, PPARG rs1801282, and rs3856806 polymorphisms were all significantly associated with individual susceptibility to PCOS in certain populations.

&lt;p&gt;Association between polymorphisms of &lt;em&gt;LEP&lt;/em&gt;,&lt;em&gt; LEPR&lt;/em&gt;, &lt;em&gt;DRD2&lt;/em&gt;, &lt;em&gt;HTR2A&lt;/em&gt; and&lt;em&gt; HTR2C&lt;/em&gt; genes and risperidone- or clozapine-induced hyperglycemia&lt;/p&gt;

ObjectiveTo determine whether genetic polymorphisms related to pharmacodynamics with metabolic adverse effects, namely leptin promoter (LEP) rs7799039, leptin receptor rs1137101, dopamine D2 rs4436578, serotonin 5-HT2A rs6313, and serotonin 5-HT2C rs518147 and rs12836771, are associated with hyperglycemia induced by risperidone or clozapine in adult Thai patients with psychosis.MethodsA total of 180 patients treated with risperidone-based (n=130) or clozapine-based (n=50) regimens were included in this study. Blood samples were analyzed for genotyping of the candidate genes and biochemical testing. Genotyping was performed by conducting a TaqMan real-time polymerase chain reaction-based analysis.ResultsThe prevalence of hyperglycemia was higher in patients receiving clozapine (64.0%) than in those receiving risperidone (30.8%). Among the candidate genes, only the LEP rs7799039 polymorphism demonstrated a significant association with hyperglycemia (χ2=9.879, P=0.008) in patients treated with risperidone; patients with the AA genotype had the highest risk (41.1%), followed by those with AG (20.8%) and GG (0%) genotypes. Using the recessive genetic model (AA vs AG + GG), the odds ratio and 95% CI were 3.28 and 1.44 −7.50, respectively. None of the genes were associated with hyperglycemia in patients treated with clozapine. A binary logistic regression revealed that the LEP rs7799039 polymorphism demonstrated a significant association with hyperglycemia, independent of body-mass index (BMI) in patients receiving risperidone; the odds ratio (95% CI) was 3.188 (1.399–7.262), P=0.006. By contrast, none of the pharmacodynamic genetic factors, except for BMI, were significantly associated with hyperglycemia in patients receiving clozapine.ConclusionThe risk of type 2 diabetes mellitus is associated with the LEP rs7799039 polymorphism in Thai adults receiving risperidone but not in those receiving clozapine. Clarifying underlying mechanisms and risk of hyperglycemia provides an opportunity to prevent impaired glucose metabolism in patients receiving risperidone or clozapine.

Investigation of leptin receptor rs1137101 G>A polymorphism with cancer risk: evidence from 35936 subjects.

Leptin receptor (LEPR) signaling may be involved in promoting angiogenesis and proliferation, inhibiting apoptosis and playing a vital role in the progression of carcinogenesis. A number of studies have focused on the association of LEPR rs1137101 variants with susceptibility of cancer, however, the observed results were controversial. We searched literature on the relationship of LEPR rs1137101 G>A polymorphism with cancer risk by using PubMed and Embase databases, covering all publications up to 14 October 2018. In total, 44 case–control studies with 35,936 subjects were included. After combining all eligible studies, we identified null relationship between LEPR gene rs1137101 G>A polymorphism and overall cancer risk [A vs. G: odds ratio (OR ) = 0.97, 95% confidence interval (CI ) = 0.89–1.06, P = 0.547; AA vs. GG: OR = 0.93, 95% CI = 0.78–1.13, P = 0.476; AA/GA vs. GG: OR = 0.99, 95% CI = 0.91–1.09, P= 0.890 and AA vs. GA/GG: OR = 0.92, 95% CI = 0.82–1.04, P= 0.198]. However, in a subgroup analysis, there was an increased susceptibility of oral and oropharyngeal cancer in AA vs. GA/GG genetic model (OR, 1.83; 95% CI, 1.01–3.33; P=0.048). Considering the limited participants were included, the findings might be underpowered. Sensitivity analysis identified that any independent study omitted did not materially influence the pooled ORs and CIs. The results of publication bias detection showed that there was no evidence of bias. In summary, this analysis indicates that no significant association of cancer risk was identified to be correlated with rs1137101 G>A variants, even in stratified analyses.

Associations of leptin and leptin receptor genetic variants with coronary artery disease: a meta-analysis.

Background: Some pilot studies already tried to investigate potential associations of leptin (LEP) and LEP receptor (LEPR) variants with coronary artery disease (CAD). However, the results of these studies were not consistent. Thus, we performed the present meta-analysis to explore associations between LEP/LEPR variants and CAD in a larger pooled population.Methods: Systematic literature research of PubMed, Web of Science, Embase and CNKI was performed to identify eligible case–control studies on associations between LEP/LEPR variants and CAD. The initial search was conducted in September 2018 and the latest update was performed in December 2018. Q test and I2 statistic were employed to assess between-study heterogeneities. If probability value(P-value) of Q test was less than 0.1 or I2 was greater than 50%, random-effect models (REMs) would be used to pool the data. Otherwise, fixed-effect models (FEMs) would be applied for synthetic analyses.Results: A total of ten studies published between 2006 and 2018 were eligible for analyses (1989 cases and 2601 controls). Pooled analyses suggested that LEP rs7799039 variant was significantly associated with CAD under over-dominant model (P=0.0007, odds ratio (OR) = 1.36, 95% confidence interval (CI): 1.14–1.63, I2 = 41%, FEM) in overall population, and this significant finding was further confirmed in East Asians in subsequent subgroup analyses. However, no positive findings were observed for LEPR rs1137100 and rs1137101 variants in overall and subgroup analyses.Conclusions: Our meta-analysis suggested that LEP rs7799039 variant might affect individual susceptibility to CAD.

Fat mass and obesity-associated (FTO) and leptin receptor (LEPR) gene polymorphisms in Egyptian obese subjects

Background Several studies addressed the contribution of fat mass and obesity-associated (FTO) and leptin receptor (LEPR) polymorphisms for the susceptibility to obesity among different ethnic subjects. The main purpose of this work is to evaluate the association of these polymorph\\isms with obesity among Egyptian subjects. Subjects and methods This case-control study was carried out on 110 unrelated obese Egyptian subjects who were compared with 122 controls. Their genomic DNA was genotyped using the PCR technique. Results The allelic frequencies of FTO rs9939609 (A) and LEPR rs1137101 (223R) were significantly higher in obese subjects compared with non-obese controls (p < .001). Comparing different phenotype frequencies including clinical, anthropometric, and biochemical parameters in obese subjects revealed no significant difference in relation to their genotype frequencies (p> .05). Conclusions This study designates a strong association for FTO and LEPR variants with the risk of obesity among Egyptian subjects.

Association of single nucleotide polymorphisms of LEPR gene with essential hypertension among ethnic Mongolian and Han Chinese from Inner Mongolia region

To assess the association of single nucleotide polymorphisms (SNPs) of leptin receptor (LEPR) gene with essential hypertension (EH) and body mass index (BMI) among ethnic Mongolian and Han Chinese from Inner Mongolia region. In total 411 Han Chinese patients with EH and 480 healthy controls, together with 658 Mongolian patients with EH and 403 healthy controls, were collected. The SNPs of the LEPR gene were determined with ligase detection reaction (LDR). Logistic regression was used to analyze the association of the polymorphisms of each locus with EH and BMI. MDR software was used to analyze the interaction between above loci and environmental factors. Genotypic frequencies of LEPR gene rs7555955, rs1137100 and rs1137101 loci had differed significantly among ethnic Hans with EH and the control group (All P<0.05). While those of rs7555955, rs1805094, rs1137100, rs11579567, rs1805134 and rs6669354 loci had differed significantly among ethnic Mongolians with EH and the control group (All P<0.05). After adjustment for confounders, logistic regression analysis indicated that age (OR=2.97, 95%CI:1.94-3.99), BMI (OR=3.93, 95%CI:2.91-5.96), and rs1137101 (AA) (OR=3.96, 95%CI:1.32-11.90) were independent risk factors for EH among ethnic Hans, while age (OR=2.99, 95%CI:2.98-4.57), BMI (OR=3.03, 95%CI:1.05-1.27), rs7555955 (AG, AA) (OR=12.12, 95%CI:2.80-52.43; OR=6.35, 95%CI:1.44-27.94), and rs7555955 (GG) were independent risk factors for EH among ethnic Mongolians (P<0.05). Age and BMI are independent risk factors for EH in both ethnic Han and Mongolian Chinese. rs1137101 locus is associated with EH among ethnic Hans, while rs7555955 locus is associated with EH among ethnic Mongolians.

Association of inflammatory genes in obstructive sleep apnea and non alcoholic fatty liver disease in Asian Indians residing in north India.

BackgroundPrevious studies have indicated that variants of the high sensitive C-reactive protein (CRP), Interleukin (IL)-6 and leptin receptor (LEPR) genes are associated with the presence of obstructive sleep apnea (OSA) but not in non-alcoholic fatty liver disease (NAFLD) in Asian Indians. The study was conducted to investigate the association of CRP rs1130864 (1444C/T), IL-6 rs1800795 (-174G/C) and LEPR rs1137101 (Q223R) genes with OSA and NAFLD in Asian Indians residing in North India.Methods240 overweight/ obese subjects [body mass index (BMI>23kg/m2)], 124 with OSA and with NAFLD (group 1), 47 with OSA without NAFLD (group 2), 44 without OSA and with NAFLD (group 3) and 25 without OSA and without NAFLD (group 4) were recruited in this study. The severity of NAFLD was based on abdomen liver ultrasound and of OSA on overnight polysomnography. Clinical details, anthropometry profile, body composition, biochemical parameters and inflammatory markers were measured. Polymerase chain reaction and restriction fragment length polymorphism of CRP, IL-6 and LEPR gene was performed. The associations of these polymorphisms with clinical, anthropometric and biochemical profiles were investigated. The genotypes were confirmed by DNA sequencing analysis.ResultsThe C, T and R alleles of IL-6, CRP and LEPR genes was more frequent in OSA and NAFLD subjects and significantly correlated with higher protein levels. The prevalence of variant genotypes C/T of CRP, G/C of IL-6 and Q/R of LEPR genes was significantly higher in OSA subjects as compared to non OSA subjects. Further, C/C genotype of IL-6 (G/C), T/T of CRP (C/T) and RR genotype of LEPR (Q/R) was associated with significantly higher BMI, fat mass (kg), % body fat, waist circumference, serum triglycerides, total cholesterol, alkaline phosphate, aspartate transaminase and fasting insulin levels in OSA and NAFLD subjects. Using a multivariate analysis, the combined effect of three polymorphisms of CRP, IL-6 and LEPR gene variants on OSA and NAFLD risk was evaluated. Odds ratio for OSA and NAFLD with the combination of the three gene polymorphisms increased to 2.84 (95% CI: 1.08–6.54; p = 0.04) even when adjusted for sex, age and BMI.ConclusionPolymorphisms of pro-inflammatory cytokine genes were associated with increased risk of OSA and NAFLD in Asian Indians.

Association of polymorphisms of leptin, leptin receptor and apelin receptor genes with susceptibility to coronary artery disease and hypertension

AimsApelin and leptin are factors which have a potential physiological and pathological role in cardiovascular homoeostasis. Apelin receptor (APLNR), leptin receptor (LEPR) and leptin variants may affect the vascular tone in heart or peripheral circulation, thereby predisposing patients to hypertension and coronary artery disease (CAD). The aim of the present study was to evaluate four single nucleotide polymorphisms (SNPs) of APLNR genes (rs11544374 and rs948847), LEPR (rs1137101) and leptin (rs7799039) gene in patients with CAD and hypertension. Materials and methodsThis case-control study was carried out on 286 CAD-suspected patients. The participants were divided into four subgroups including: CAD patients with no hypertension (H−CAD+), hypertensive patients with no CAD (H+CAD−), CAD patients with hypertension (H+CAD+) and non-hypertensive non-CAD subjects as control group (H−CAD−). Genomic DNA from whole blood was extracted and four SNPs were assessed using PCR-RFLP. Key findingsA significant difference was found in the genotype frequency of APLNR rs11544374 gene in H+CAD+ and H−CAD+ groups compared to control subjects (P < 0.001 for both comparisons). Regarding the rs1137101, the prevalence of A allele compared to G allele was significantly different among the four groups (P = 0.02). Results of multinomial regression analysis indicated that G allele carriers in the recessive genetic model (AA vs. AG + GG) of rs11544374 had a significantly protective effect compared to H−CAD+ and H+CAD+after adjustment (OR = 0.12; 95% CI = 0.02–0.61; P = 0.01 and OR = 0.40; 95% CI = 0.17–0.98; P = 0.04, respectively). SignificanceThe findings of present study revealed that the APLNR rs11544374 gene polymorphism might serve as predisposing factor in CAD.

Association between LEPR, FTO, MC4R, and PPARG-2 polymorphisms with obesity traits and metabolic phenotypes in school-aged children

PurposeEvaluate the relationship of leptin receptor (LEPR) rs1137101, fat mass obesity-associated (FTO) receptors 9939609, melanocortin-4 receptors (MC4R) rs2229616 and rs17782313, and proliferator-activated receptor-gamma (PPARG) rs1801282 with clinical and metabolic phenotypes in prepubertal children.Research questionWhat is the effect of polymorphisms on clinical and metabolic phenotypes in prepubertal children?MethodsA cross-sectional descriptive study was performed to evaluate anthropometric features, percentage body fat (%BF), biochemical parameters, and genotype in 773 prepubertal children.ResultsFTO rs9939609 was associated with an increase in body mass index (BMI) and BMI z-score (zBMI). MC4R rs17782313 was associated with a decrease in BMI and +0.06 units in zBMI. LEPR, and PPARG-2 polymorphisms were associated with decreases in BMI and an increase and decrease units in zBMI, respectively. The homozygous SNPs demonstrated increases (FTO rs993609 and MC4R rs17782313) and decreases (LEPR rs1137101, PPARG rs1801282) in zBMI than the homozygous form of the major allele. In the overweight/obese group, the MC4R rs17782313 CC genotype showed higher average weight, zBMI, waist circumference, waist-circumference-to-height ratio, and waist-hip ratio, and lower BMI, mid-upper arm circumference, calf circumference, and %BF (P< 0.05). FTO rs9939609 AT and AA genotypes were associated with lower triglycerides (P < 0.05).ConclusionsWe showed that MC4R rs17782313 and FTO rs9939609 were positively associated with zBMI, with weak and very weak effects, respectively, suggesting a very scarce contribution to childhood obesity. LEPR rs1137101 and PPARG-2 rs1801282 had weak and medium negative effects on zBMI, respectively, and may slightly protect against childhood obesity.

Genetic polymorphisms of HTR2C, LEP and LEPR on metabolic syndromes in patients treated with atypical antipsychotic drugs.

Single nucleotide polymorphisms in serotonin 2C receptor (HTR2C), leptin (LEP), and leptin receptor (LEPR) genes are reportedly associated with the presence of metabolic syndrome (MS). We investigated whether HTR2C:rs518147 (-697G/C), rs12836771 (A/G), LEP: rs7799039 (-2548G/A) and LEPR:rs1137101 (668A/G) are related to MS in psychotic disorder patients treated with atypical antipsychotics. A cross-sectional study including 200 patients was conducted; genetic polymorphisms in HTR2C (rs518147 and rs12836771), LEP (rs7799039) and LEPR (rs1137101) were genotyped. The presence of MS was evaluated according to the 2005 International Diabetes Federation (IDF) Asia criteria. The associations of genetic factors with the presence of MS are analysed. Two SNPs in the HTR2C gene but not LEP and LEPR were associated with the presence of MS after adjustment for the combination of atypical antipsychotics. With respect to the effect of gender after treatment with risperidone and clozapine was statistically significant. Moreover, genotype combinations had no effect on MS. Therefore, HTR2C genetic variants may be involved in the susceptibility to MS in patients treated with atypical antipsychotics. Additionally, there was a gender effect in the presence of MS. No effect of LEP or LEPR polymorphisms or the combination of HTR2C-LEP and HTR2C-LEPR was observed for the presence of MS.

Investigation of TCF7L2, LEP and LEPR polymorphisms with esophageal squamous cell carcinomas.

Single nucleotide polymorphisms (SNPs) in energy metabolism related gene may be key agents in the development of human malignancies. In this study, we aimed to examine the association of transcription factor 7-like 2, Leptin (LEP) and LEP receptor (LEPR) polymorphisms with esophageal squamous cell carcinoma (ESCC). A total of 507 ESCC cases and 1,496 controls were enrolled. We found that LEPR rs6588147 AA genotype was associated with ESCC risk (AA vs. GG/GA: adjusted OR=1.90, 95%CI=1.00–3.61, P=0.049). In the stratified analyses, LEPR rs6588147 G>A polymorphism increased the risk of ESCC (<63 years subgroup: AA vs. GG: adjusted OR=2.58, 95%CI=1.00–6.62, P=0.049 and AA vs. GA/GG: adjusted OR=2.71, 95%CI=1.06–6.91, P=0.038; male subgroup: AA vs. GG: adjusted OR=2.19, 95%CI=1.02–4.67, P=0.044 and AA vs. GA/GG: adjusted OR=2.26, 95%CI=1.06–4.80, P=0.035). However, LEP rs7799039 A>G decreased the risk of ESCC (≥63 years subgroup: GG vs. AA: adjusted OR=0.47, 95%CI=0.23–0.95, P=0.035 and GG vs. AA/AG: adjusted OR=0.48, 95%CI=0.24–0.96, P=0.038; BMI≥24 kg/m2 subgroup: AG vs. AA: adjusted OR=0.66, 95%CI=0.45–0.99, P=0.044). In addition, LEPR rs1137101 G>A polymorphism decreased ESCC risk in some subgroups (ever smoking subgroup: GA vs. GG: adjusted OR=0.66, 95%CI=0.44–1.00, P=0.049; ever drinking subgroup: GA vs. GG: adjusted OR=0.54, 95%CI=0.31–0.95, P=0.031 and GA/AA vs. GG: adjusted OR=0.54, 95%CI=0.31–0.93, P=0.027). Our findings suggest that LEPR rs6588147 G>A polymorphism is associated with the increased risk of ESCC; however, LEP rs7799039 A>G and LEPR rs1137101 G>A polymorphisms may be protective factors for ESCC.

Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in gestational diabetes in a Brazilian population.

Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®). All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%] and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37-49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%], respectively. The studied polymorphisms were not associated with GDM in a Brazilian population.