Leptin Receptor Polymorphisms Research Articles

Leptin and leptin receptor gene polymorphisms and depression treatment response.

Associations between leptin (LEP) and leptin receptor (LEPR) gene polymorphisms and mood disorders have been found but not yet confirmed in multiple studies. The aim of our study was to study the associations between LEP and LEPR single nucleotide polymorphisms (SNPs) and treatment response of depression. Associations between leptin levels and depression severity were also investigated. The data included 242 depressed patients in secondary psychiatric care. Symptoms of depression were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS). Previously found LEP and LEPR SNPs associated with depression and other mood disorders were studied. Furthermore, all available LEP and LEPR SNPs were clumped using proxy SNPs to represent gene areas in r2 > 0.2 linkage disequilibrium and their association with treatment response was analysed with logistic regression. Two proxy SNPs of LEPR gene, rs12564738 and rs12029311, were associated with MADRS response at 6 weeks (p adjusted = 0.024, p adjusted = 0.024). SNPs from previous studies were not associated with MADRS response, but LEPR rs12145690 from a previous study was strongly associated with rs12564738 (r2 = 0.94). The positive association between leptin levels and MADRS score at baseline after adjusting with age, sex, body mass index (BMI), Alcohol Use Disorders Identification Test score, and smoking was found (p = 0.011). Our findings suggest that LEPR polymorphisms are associated with depression treatment response. We also found associations between leptin levels and depression independently of BMI. Further studies and meta-analyses are needed to confirm the significance of found SNPs and the role of leptin in depression.

Association between some Serum Parameters in Iraqi Women with Polycystic Ovary Syndrome and leptin receptor gene polymorphism

Polycystic ovarian syndrome (PCOS) is considered as a complex, heterogeneous disorder that impacts 5-10% of women at reproductive age. This study aimed to evaluate the association of leptin recepter gene polymorphism (Lys109Arg, rs1137100) and some serum parameters with PCOS in of Iraqi women. This case-control study was carried out during the period from July to October, 2022 at Infertility Care and IVF center of Kamal AL-Samaraay Hospital, Baghdad. The study included 120 Iraqi women as a sample size divided into two groups 60 PCOS patients and 60 apparently healthy control. PCOS patients were diagnosed by gynecologists according to Rotterdam criteria. The genotypes of leptin receptor gene at rs137100 SNP were determined by using HRM-PCR. The serum levels of leptin, soluble leptin receptor (sOB-R) and AMH were measured by using Elisa kits. Lipid profile parameters were measured by spin 200 full auto. LH, FSH, testosterone, estradiol, progesterone, TSH, T3 and T4 hormones were measured by cobas E411. Results revealed that BMI values were significantly increased (p≤0.01) in PCOS patients compared to controls (30.21±0.70 versus 24.28±0.617). Serum leptin and sOB-R levels were significantly (p˂0.05) higher in PCOS patients than controls (4303.28±71.55 versus 3854.84 ±213.96 pg /ml and 144.09 ±5.51 versus 122.16 ±7.64 ng/ml respectively). The frequency of AA genotypes was significantly (p˂0.05) lower in PCOS patients than in apparently healthy subjects (33.3 % versus 65.0% respectively) whereas the frequencies of AG and GG genotypes were significantly (p˂0.05) higher in PCOS patients versus controls (53.3% versus 26.6% and 13.4% versus 8.4% respectively).The A allele frequency was higher in apparently healthy subjects than in PCOS women (78.3% versus 60.0% respectively) while G allele frequency was significantly higher in PCOS patients versus controls (80.0% versus 21.7%, respectively). It was concluded that the leptin receptor polymorphism (rs1137100) is strongly linked to an increased risk of developing PCOS. Further, those with the A allele are less likely to develop PCOS.

Leptin receptor Gln223Arg and Lys109Arg polymorphisms may be associated with HBV-related hepatocellular carcinoma risk: A system review and meta-analysis.

Increasing evidence has suggested a strong association of hepatocellular carcinoma (HCC) susceptibility and Gln223Arg (rs1137101) and Lys109Arg (rs1137100) polymorphisms in leptin receptor (LEPR) genes. To provide a quantitative assessment for such correlation, we reviewed all related systems and conducted meta-analysis for case and control researches. A literature search of Web of Science, EMBASE, PubMed, Scopus as well as China National Knowledge Infrastructure databases was collected. 95% confidence intervals (95% CIs) together with odds ratios (ORs) were calculated. Five case-control researches consisting of 1323 cases and 1919 control cases were incorporated into meta-analysis. Researches indicated A-allelic and AA genotype of rs1137101 were substantially related to boosted susceptibility of hepatitis B virus (HBV)-related HCC (mutant model, OR = 1.81, 95% CI = 1.36-2.41, p < .001; allelic model, OR = 1.55, 95% CI = 1.32-1.83, p < .001). On the contrary, we observed GG genotype of rs1137101 substantially related to reduced risk of HBV-related HCC (wild model, OR 0.59, 95%CI = 0.46-0.75, p < .001). We observed AA genotype of rs1137100 relevant to boosted HCC risk (mutant model, OR = 1.51, 95%CI = 1.14-2.01, p = .005) as well as in those with HBV-related HCCs (homozygous model, OR = 2.12, 95%CI = 1.49-3.02, p < .001; mutant model, OR = 1.67, 95%CI = 1.23-2.26, p = .001). G-allele and AA genotype of rs1137101 might be in connection with boosted HBV-related HCC susceptibility, and wild-type GG genotype might prevent diseases. AA genotype of rs1137100 might also improve HBV-related HCC susceptibility. Such conclusions ought to be validated by larger and better-designed researches.

Association of leptin receptor polymorphisms with susceptibility of non-small cell lung cancer: Evidence from 2249 subjects.

Non-small cell lung cancer (NSCLC) is increasing dramatically. It is believed that energy metabolism-related genes could play an important role in etiology of NSCLC. In this study, we sought to assess the correlation between three LEPR single nucleotide polymorphisms (rs1137101, rs1137100 and rs6588147) with NSCLS susceptibility. In total, 1193 NSCLC cases and 1056 controls were included. SNPscan™ genotyping method was used to analyze the genotypes of LEPR polymorphisms. Compared to rs6588147 GG in LEPR gene, this study identified a protective role of LEPR rs6588147 GA and GA/AA for the occurrence of NSCLC (GA vs. GG [p = 0.021] and GA/AA vs. GG [p = 0.030]). As well, we found that a protective role of LEPR rs6588147 for the occurrence of non-SCC subgroup (p < 0.05). By logistic regression analysis, we found that the rs6588147 A allele related genotypes might play a protective role for the occurrence of NSCLC in drinking, BMI ≥24 kg/m2, smoking and male subgroups. We also found that the rs1137101 A allele related genotypes played a protective role for the occurrence of NSCLC in male, younger participants (under 59 years) and overweight/obesity (BMI ≥24 kg/m2) subgroups. We found that LEPR Ars1037100Ars1037101Ars6588147 haplotype might play a protective role for the occurrence of NSCLC (p = 0.013). In addition, our findings indicated that LEPR rs1137100 G>A SNP might increase the risk of lymph node metastases (p = 0.038). This study highlights that LEPR rs6588147, rs1137101 genotypes and LEPR Ars1037100Ars1037101Ars6588147 haplotype are correlated with the occurrence of NSCLC. LEPR rs1137100 G>A SNP increases the risk of lymph node metastases.

Leptin and Leptin Receptor Polymorphisms in Infants and Their Parents: Correlation with Preterm Birth.

It has been proven that single-nucleotide polymorphisms (SNPs) in LEP and LEPR genes could predispose individuals to an increased risk of pregnancy adverse outcomes (PAOs) such as recurrent pregnancy loss (RPL) and pre-eclampsia. Preterm birth (PTB) is the leading cause of infant mortality. We decided to investigate the correlation between PTB and LEP and LEPR SNPs. The study cohort included families who underwent spontaneous PTB and control samples of families who had at-term-born (≥37 weeks of gestational age) children. Swabs were performed by rubbing the sticky end for about 30 s on the gum and on the inside of the cheek, allowing us to collect the flaking cells of the oral mucosa. Genotyping of the three SNPs-LEPRA668G, LEPG2548A and A19G-was carried out via an ARMS-MAMA real-time PCR procedure, as previously described. Regarding LEPG2548A, we found that the most expressed genotype in infants both in the preterm and the at-term group was AG; however, we did not discover any statistically significant difference (p = 0.97). Considering LEPA19G, none among the infants and parents were found to carry the AA genotype. No statistically significant differences were found between children, mothers and fathers belonging to preterm and at-term groups. We did not find a statistically significant association in newborns and their mother, but our results show a statistical correlation with the LEPRA668G genotype GG of the father. This fact can contribute to defining genetic risk factors for PTB. Further studies are certainly needed to better clarify the role of genetics in influencing preterm delivery.

Enlightening the Correlation of Polymorphisms at FTO, LEP and LEPR Genes with Gestational Diabetes Mellitus Risk: a Meta-analysis

Background: The adverse outcomes correlated with GDM for both the mother and the offspring are diverse. The link between polymorphisms at fat mass and obesity‐correlated protein (FTO), leptin (LEP), and leptin receptor (LEPR) genes and GDM is ambiguous. In this meta-analysis, we sought to investigate the correlation of FTO, LEP, and LEPR polymorphisms with GDM risk.&#x0D; Methods: We performed an online search on PubMed, Web of Science, and Google Scholar databases to identify all relevant research.&#x0D; Results: A total of 18 case-control studies including seven research with 893 cases and 2875 controls on FTO rs9939609, four research with 1345 cases and 1116 controls on FTO rs8050136, two research with 207 cases and 205 controls on FTO rs1421085, three studies with 529 cases and 581 controls on LEP rs7799039, and two research with 480 cases and 477 controls on LPER rs1137101 met our criteria. Combined data illustrated that the FTO rs9939609 and rs8050136 were correlated with a substantial risk of GDM in the overall population, but not FTO rs1421085. Furthermore, LEP rs2167270 and rs7799039 polymorphisms were not correlated with GDM risk. Sorted analyses illustrated that the FTO rs9939609 polymorphism was correlated with GDM in Caucasian women.&#x0D; Conclusion: This meta-analysis results illustrated that the FTO rs9939609 and rs8050136 were correlated with a substantial risk of GDM, but not FTO rs1421085, LEP rs7799039, and LPER rs1137101. Larger and more rigorous studies among different ethnicities are needed to further evaluate the correlations with GDM.

Association between leptin receptor polymorphisms and polycystic ovary syndrome risk: a meta-analysis based on 11 studies

Objective Published evidence indicated that the leptin receptor (LEPR) gene polymorphisms are associated with polycystic ovary syndrome (PCOS) risk. However, studies on the association between the polymorphisms of LEPR gene are inconsistent or even controversial. Material and Methods We conducted this meta-analysis to explore the more precise relationship between LEPR polymorphisms and PCOS risk. Relevant articles were searched with five online databases up to March 1 2023. Odds ratios (OR) with 95% confidence intervals (CI) were selected to examine the statistical strength of each genetic model. Moreover, RNA secondary structure and variant effects of these loci were examined with in silico analysis. Results Overall, 11 publications were analyzed, and the pooled results did not present any significant association between rs1137101 A/G polymorphism and PCOS risk in general population and some subgroup analysis. But the significant association were observed in Asian population (AG vs. AA: OR = 0.51, 95%CI = 0.32–0.81, p = .01, I2=0%; AG + GG vs. AA: OR = 0.41, 95%CI = 0.26–0.65, p < .01, I2=25.9%). Moreover, similar positive associations were also observed in rs1805096 polymorphism with PCOS risk. Conclusion In summary, our meta-analysis suggested that the LEPR gene polymorphisms might be associated with PCOS susceptibility. Owing to the limited studies and small sample size in our meta-analysis, more well-designed studies from different races were needed to be conducted to verify the current results.

Associations between polymorphisms in leptin and leptin receptor genes and colorectal cancer survival.

Leptin (LEP) is an obesity-associated adipokine associated with tumor cell growth. We examined the relevance of genetic variants of LEP and leptin receptor (LEPR) to colorectal cancer (CRC) survival by using data from the Newfoundland Familial Colorectal Cancer Study. A total of 532 patients newly diagnosed with CRC between 1997 and 2003 were followed up until April 2010. Data on their demographics and lifestyles were collected via questionnaires. Genotyping of blood samples was performed with the Illumina Human Omni-Quad Bead chip. Multivariable Cox models were used to assess the relationships of 35 tag single-nucleotide polymorphisms (SNPs) in LEP and LEPR with overall survival (OS), disease-free survival (DFS), and CRC-specific survival. At the gene level, LEP was associated with DFS (P = 0.017), and LEPR was associated with both DFS (P = 0.021) and CRC-specific survival (P = 0.013) in patients with CRC. In single-SNP analysis, LEP rs11763517, LEPR rs9436301, and LEPR rs7602 were associated with DFS after adjustment for multiple testing. The LEPR haplotypes G-C-T (rs7534511-rs9436301-rs1887285) and A-A-G (rs7602-rs970467-rs9436748) were associated with prolonged OS among patients with CRC overall (G-C-T: HR, 0.63; 95% CI, 0.43-0.93; A-A-G: HR, 0.59; 95% CI, 0.38-0.91) and those diagnosed with colon cancer (G-C-T: HR, 0.54; 95% CI, 0.34-0.86; A-A-G: HR, 0.49; 95% CI, 0.29-0.83). Similar results were observed for DFS. Moreover, significant interactions were found among LEPR rs7602 (A vs. G), LEPR rs1171278 (T vs. C), red meat intake, and BMI status: the associations between these variants and prolonged DFS were limited to patients with below-median red meat consumption and body mass index (BMI) < 25 kg/m2. Polymorphic variations in the LEP and LEPR genes were associated with survival of patients after CRC diagnosis. The LEP/LEPR-CRC survival association was modified by participants' red meat intake and BMI.

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.

Association between genetic polymorphisms of leptin receptor and preeclampsia in Chinese women

Objective Leptin signaling plays an important role in regulating metabolism and reproduction. In the present study, we investigated the relationship between polymorphisms of leptin receptor (LEPR) gene A223G and A668G and preeclampsia (PE) and evaluated influences of genotypes on clinical, metabolic, and oxidative stress indices in Chinese women. Methods This is a case-control study including 322 patients with PE and 1295 healthy pregnant women. The two polymorphisms were genotyped by polymerase chain reaction-restriction fragments length polymorphism method. Clinical and biochemical parameters were analyzed. Results The frequencies of the AA + AG genotypes (28.6% vs. 36.1%) and A allele (14.9% vs. 19.8%) of LEPR A223G polymorphism, and those of the AA + AG genotypes (17.7% vs. 24.6%) and A allele (9.0% vs. 12.9%) of LEPR A668G polymorphism were significantly lower in the PE group than those in the control group. The 223A and 668A alleles were protective factors against PE in the regression model, which included age and delivery body mass index as covariates (OR = 0.684, 95% CI: 0.506–0.926, p = .014; OR = 0.650, 95% CI: 0.456–0.927, p = .017, respectively). When the 668GG/223GG combined genotype served as the reference category, the 668A/223A combined allele had further enhanced the protective effect on PE (OR = 0.558, 95% CI: 0.374–0.833, p = .004). Patients possessing the LEPR 223A allele had higher total antioxidant capacity and lower oxidative stress index (p < .05), while those with the LEPR 668A allele had higher high-density lipoprotein cholesterol levels (p = .045) compared with those carrying the corresponding GG genotype. Conclusions The 223A and 668A alleles of LEPR polymorphisms are genetic protective factors for PE in Chinese women. The two alleles may exert a beneficial effect on oxidative stress and lipid metabolism in patients.

Prospective Role of Leptin Receptor Gene and its Polymorphisms on the Onset of Polycystic Ovarian Syndrome

Introduction: Leptin hormone is produced by adipose tissue and soluble leptin receptor (sOB-R) influences leptin's free bioavailability. Obese individuals have unusually elevated leptin levels. Obesity influences insulin and other hormone levels and is a key risk factor for developing polycystic ovarian syndrome (PCOS) and mutations such as rs2025804 and G2548A (rs7799039). PCOS is a hormonal condition that affects females of reproductive age primarily. Although there is no known cause of PCOS, studies have linked it to various factors, including insulin resistance, obesity, and genetics. Till now, research indicates a substantial correlation between leptin and female reproductive hormones, and PCOS. Thus, the purpose of this study is to compile the available data for a better understanding of the link between leptin and its effect on female reproductive hormones and PCOS and to determine whether the leptin receptor polymorphism (LEPR) influences the start of PCOS. Methods: Following a review of the relevant papers, it was determined that there is an association between leptin and female reproductive hormones such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), progesterone, and prolactin. It was observed that Gln223Arg (Q223R/rs1137101), Pro1019Pro (A3057G), Lys109Arg (K109R/rs1147100), rs2025804, and G2548A (rs7799039) are the LEPR polymorphisms associated with PCOS. Gln223Arg is the most frequently studied variant in the LEPR gene across populations. Results: Interestingly, different groups demonstrated varying relationships between leptin receptor polymorphisms and PCOS, particularly for Gln223Arg, which contains two alleles (G allele and A allele). The G allele was protective against PCOS in the Korean population but increased the frequency of PCOS in countries such as Bahrain, India, Iran, and Iraq. There was no significant difference between PCOS and controls with this polymorphism in places such as China, Turkey, Saudi Arabia, and Helsinki. Conclusion: To summarize, the association between multiple leptin receptor polymorphisms and PCOS is complex and varies by research region. There hasn't been much research done on the gene polymorphism "Gln223Arg" or the other polymorphisms. While certain research findings were notable, each came with its limitations. As a result, additional interventional studies, including precise criteria in bigger and more diverse groups, are required.

Correlation of Q223R and K109R polymorphisms in leptin receptor gene with susceptibility of breast cancer: A systematic review and meta-analysis.

Increasing evidence has suggested a strong association of Q223R (rs1137101) and K109R (rs1137100) polymorphisms in leptin receptor (LEPR) gene with susceptibility of breast cancer (BC), but inconsistent results were obtained. To provide a quantitative assessment of this association, a systematic review and meta-analysis was performed. A literature search of PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure was collected. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. A total of 20 case-control studies for Q223R polymorphism and 8 case-control studies for K109R polymorphism were included. Significant association between Q223R polymorphism and BC risk was not found in total, Asian or Caucasian population, but in African population: allelic model, OR = 0.72, 95% CI = 0.60-0.86, p < 0.001; recessive model, OR = 0.67, 95%CI = 0.52-0.87, P = 0.003; dominant model, OR = 1.58, 95% CI = 1.15-2.17, p = 0.004; homozygous model, OR = 0.51, 95% CI = 0.36-0.78, p < 0.001. Significant association between K109R polymorphism and BC risk was not found in total or Caucasian population, but in Asian population: dominant model, OR = 0.24, 95% CI = 0.07-0.84, p = 0.03; heterozygous model, OR = 1.87, 95% CI = 1.07-3.26, p = 0.03. The available evidence suggests that Q223R polymorphism may be significantly associated with BC risk in African population. K109R polymorphism may be significantly associated with BC risk in Asian population.

GHRL, LEP, LEPR genes polymorphism and their association with the metabolic syndrome in the Ukrainian population.

Objective. Many conflicting results have been obtained in the study of leptin (LEP) and leptin receptor (LEPR) gene variants that are associated with the obesity and diabetes possibly due to differences in the study populations. The aim of this study was to evaluate changes in the metabolic hormones (leptin, ghrelin, adiponectin, resistin) levels in the blood of obese patients in relation to the GHRL (rs696217), LEP (rs7799039), LEPR (rs1137100, rs1137101, rs1805094) polymorphism in Ukrainian population. Methods. The study involved 53 obesity cases and 48 non-obesity subjects (controls). The GHRL, LEP, and LEPR genes polymorphism (rs696217, rs7799039, rs1137100, rs1137101, rs1805094) was genotyped using a TaqMan real-time polymerase chain reaction method. Blood hormones (leptin, ghrelin, adiponectin, resistin) were determined with commercially available kits using a Multiskan FC analyzer. Results. The study of the effect of genotypes of the GHRL (rs696217), LEP (rs7799039), and LEPR (rs1137100, rs1805094) polymorphisms on the level of metabolic hormones (leptin, ghrelin, adiponectin, resistin) in the blood of obese patients did not show reliably significant results. Thus, the presence of the LEPR genes (rs1137101) polymorphism in the Ukrainian population indicates an increased risk of the metabolic syndrome development regardless of the homozygous or heterozygous genotype (genotypes AA, AG, GG). Conclusions. We established a significant effect of the presence of the A allele and G allele of the LEPR gene polymorphism (rs1137101) on the level of leptin, ghrelin, adiponectin, and resistin in the serum of patients diagnosed with the metabolic syndrome in the Ukrainian population.

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.

The Effects of BMI and Genetic Variation of Adipokines on Serum Concentrations of Hormones in Untreated Individuals with Breast Cancer; a Pilot Study

Background: Numerous studies have shown an association between hormones secreted by adipose tissues and cancer development. Objectives: This study aimed at investigating the effect of body mass index (BMI) and genetic variation of leptin and adiponectin on serum concentrations of leptin, adiponectin, and estradiol among untreated breast cancer. Methods: This case-control study was performed on 350 women (175 women with breast cancer and 175 healthy controls), who had not taken any medications. Serum levels of estradiol (17-beta estradiol), leptin, and adiponectin were measured, using the ELISA technique. Single-nucleotide polymorphisms of leptin gene (LepG2548A), leptin receptor (Q223, K109R, and K656N), and adiponectin gene (T45G, G276T, C11377G, and 11391A) in blood-isolated DNA were evaluated, using RFLP-PCR technique. Results: Body mass index can affect serum concentrations of hormones and is associated with breast cancer. Also, except for adiponectin C11377G polymorphism, other all genetic variations showed significant relationships with breast cancer. In both groups, BMI was significantly correlated with the mean serum concentrations of hormones, and the risk of breast cancer increased in G2548A, Q223R, K656N, and G276T polymorphisms. The effect of risk allele genotypes on serum concentration of hormones showed that changes in serum concentration of estrogen and leptin in all studied polymorphisms were associated with breast cancer in postmenopausal women. But adiponectin level was only affected by polymorphisms K109R, K656N, and G276 and G11391A. Conclusions: High BMI and genetic variation can affect cancer development by changing the serum concentrations of hormones in different genotypes. Studying various populations’ genetics and lifestyle can help definitive conclusions about genetics and obesity.

Association study of leptin receptor polymorphisms in women with obesity and their impact on protein domains: a case-control study and in silico analyses

Leptin receptor (LEPR) is a member of the class I cytokine receptor family that receives and transmits leptin signals. It is primarily involved in the regulation of energy expenditure and food intake. This study aimed to evaluate the association of LEPR gene polymorphisms, Lys109Arg, Gln223Arg and Lys656Asn, with obesity in Moroccan women and to explore the structural and functional consequences of these SNPs. The variants were genotyped using the Sanger sequencing method. The three-dimensional structures of LEPR extracellular domains were determined using a template-based tertiary structure modeling web server and the protein variants were generated using in silico mutagenesis. The amino acids conservation analysis in the variants region was performed based on a protein’s evolutionary profile. The molecular dynamics simulations of the wild-types and variants N-terminal, cytokine receptor homology I and fibronectin type III domains of LEPR protein were performed to investigate their impact on the domain structures. We identified that only Lys656Asn polymorphism is associated with obesity in Moroccan women (P = 0.024). In silico analyses revealed that Lys109, Gln223 and Lys656 are exposed residues and their substitution leads to changes in protein structure through loss or gain of hydrogen bonds and hydrophobic interactions. Lys656Asn increases the stability and decreased flexibility of the fibronectin type III domain. Lys109Arg highly decreases the stability and increases flexibility and the overall dimension of N-terminal and cytokine receptor homology I domains. Gln223Arg increases the stability and the compaction level of these domains. These results provide insight into the involvement of LEPR variants in obesity development. Communicated by Ramaswamy H. Sarma

Association between Leptin (G2548A) and Leptin Receptor (Q223R) Polymorphisms with Plasma Leptin, BMI, Stress, Sleep and Eating Patterns among the Multiethnic Young Malaysian Adult Population from a Healthcare University.

Relative leptin resistance in childhood to absolute leptin resistance in maturity suggests sleep, eating behaviour, and the psychological state as probable causes. The current body of research provides inconclusive evidence linking G2548A and Q223R to obesity. Furthermore, we could find very little data that have observed the association between the environment and gene polymorphism, especially in the multiethnic population that exists in Malaysia. This study searched for a possible link between sleeping habits, eating behaviour, and stress indicators with plasma leptin and its genetic variation in young adult Malaysian healthcare students. The study involved 185 first- and second-year medical and dental students from a healthcare university. Polymerase Chain Reaction–Restriction Fragment Length Polymorphism(PCR-RFLP) determined the genotype, Enzyme Linked Immunoabsorbant Assay (ELISA) tested the serum leptin, and a self-administered questionnaire evaluated sleep, eating behaviour, and psychological condition. Gender and ethnicity are linked to fasting plasma leptin levels (p < 0.001). Plasma leptin also affects stress, anxiety, and sadness. Leptin (LEP) and Leptin Receptor (LEPR) polymorphisms were not associated with BMI, plasma leptin, sleep, eating behaviour, or psychological state. Young adult Malaysian Indians were obese and overweight, while Chinese were underweight. These findings imply overweight and obese participants were in stage I of leptin resistance and lifestyle change or leptin therapy could prevent them from becoming cripplingly obese as they age.

Association between LEPR polymorphism and susceptibility of osteoporosis in Chinese Mulao people

To explore the association between the single nucleotide polymorphism (SNP) of leptin receptor (LEPR) gene and the susceptibility to osteoporosis (OP) among Chinese Mulao people. A total of 738 people were involved. Bone mineral density (BMD) was examined by calcaneus ultrasound attenuation measurement. Six SNPs of LEPR were detected. The genotypes, allele frequencies, linkage disequilibrium, and haplotype were analyzed. BMD decreased with age and males had higher BMD than women. The proportion of normal bone mass decreased with age, and morbidity of OP increased. Three out of six SNPs showed a difference between OP and normal group. Individuals with AA genotype of rs1137100 in OP group outnumber the normal group, AA increased the risk of OP. In rs2767485, CT increased the risk of OP, C allele may be susceptible to OP. TT genotype of rs465555 was susceptible genotype of OP, T locus may be associated with OP. Strong linkage disequilibrium was detected among rs1137100, rs1137101, and rs4655555. Four haplotypes were constructed, among which, AACGCT and GGTGTA increased the risk of OP by 3.9 and 4.2 times, respectively, whereas, GGCGTA reduced 74% of OP susceptibility. The rs1137100, rs2767485, and rs465555 of LEPR were associated with OP in Chinese Mulao people.

Association of Leptin Receptor Q223R Gene Polymorphism and Breast Cancer Patients: A Case Control Study.

Introduction:Leptin is a hormone secreted from adipocytes that regulates metabolism and energy homeostasis through the leptin receptor (LEPR). The aim of this study was to investigate the association of leptin receptor gene Q223R gene polymorphism, and plasma leptin level among obese breast cancer females. Materials and Methods:The study enrolled 160 breast cancer patients and 160 healthy control females. LEPR Q223R polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum leptin was determined using enzyme-linked immunosorbent assay human leptin kit. Immunohistochemical tests from paraffin blocks were carried out for estrogen and progesterone staging using the precise antibodies. Results:An association was found between LEPR gene Q223R gene polymorphism among obese breast cancer females. Statistical difference was found between GG (60.6%) Arg/Arg genotype (OR=2.986; 95%CI=1.540 to 5.789; p= 0.001) compared to AA (33.1%) Gln/Gln genotype. GG Q223R LEPR polymorphism showed statistically significant difference among obese breast cancer patients (BMI more than 25) compared to control (P < 0.0001). GG genotype of Q223R LEPR polymorphism showed statistically significant increased leptin level (p-value =0.0001) among obese patients (mean± SD; 23.39±4.32) compared to control (17.83±5.67). Conclusions:Q223R LEPR polymorphism GG genotype was associated with increased leptin profile among obese breast cancer females.

Effects of genetic polymorphisms in body mass index according to dietary exposure to bisphenols and parabens

A growing body of evidence supports that more than 900 single nucleotide polymorphisms (SNPs) and exposure to endocrine disrupting chemicals, such as bisphenols and parabens, are important contributors to the development of obesity. The aim of this study was to evaluate the way in which fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs9436303 variants contribute to variability in body mass index (BMI) according to estimated dietary exposure of bisphenols and parabens. This cross-sectional study included 101 Spanish participants (16–24 years). SNP genotyping assays were performed through quantitative PCRs (qPCRs) using Taqman® probes. Dietary exposure to bisphenols and parabens was calculated from food frequency questionnaire and chemical determination in food samples by ultra-high performance liquid chromatography-tandem mass spectrometry system. Linear regression models were conducted to address the association of genetic variants and BMI according to levels of bisphenols/parabens exposure. Risk G allele of LEPR rs9436303 was significantly positively associated with BMI (exp (β) = 1.20, 95% CI: 1.04–1.38, p = 0.011). In participants highly exposed to bisphenols, the LEPR rs9436303 G allele was related to a significant increased BMI (exp (β) = 1.27, 95% CI: 1.03–1.57, p = 0.024). A more relevant trend was observed with high exposure to parabens (exp (β) = 1.33, 95% CI: 1.08–1.63, p = 0.009). We provide the first evidence that interaction between LEPR polymorphism and dietary intake of bisphenols and parabens may be responsible for an increased BMI, suggesting a potential effect in obesity. Moreover, we proposed LEPR rs9436303 as a genetic marker of susceptibility to excess weight induced by exposure.