Leptin Receptor Gene Polymorphisms Research Articles

Genetic variation in leptin and leptin receptor genes is a risk factor for idiopathic recurrent spontaneous abortion.

AimTo determine whether maternal leptin (LEP) and leptin receptor (LEPR) gene polymorphisms are associated with idiopathic recurrent spontaneous abortion (IRSA).MethodsThis case-control association study conducted from 2010 to 2012 at the Department of Gynecology and Obstetrics, University Hospital Center Osijek and Clinical Institute of Medical Genetics Ljubljana included 178 women with a history of three or more IRSAs before the 22nd week of gestation and 145 women with at least two live births and no history of pathologic pregnancies during reproductive period. Polymorphisms of maternal LEP (rs7799039, rs2122627, rs11761556, rs10244329) and LEPR (rs1137101, rs7516341, rs1186403, rs12062820) were assessed by allele specific real-time polymerase chain reaction. Genotype distribution, allele frequencies, and frequency of haplotypes at LEP and LEPR genetic loci were determined.ResultsWe observed more frequent genotype for rs7516341 (nominal P = 0.034, odds ratio [OR] 0.61, 95% confidence interval [CI] 0.38-0.97) and rs1137101 (nominal P = 0.048, OR 1.66, 95% CI 1.00-2.80) in the LEPR gene in patients than in controls, but these results did not remain significant after correction for multiple testing according to Bonferroni (adjusted P value threshold was set at 0.05). We did not observe differential distribution of genotype frequencies in the LEP gene between cases and controls. In patients with IRSA, GTCC haplotype in the LEPR gene locus was significantly less frequent than in controls (P = 0.00865, OR 0.45), contrary to ACTC haplotype (P = 0.0087, OR 1.98).ConclusionsWe showed that genetic variability in the LEPR gene was associated with IRSA, warranting confirmation on a greater number of patients and pathogenesis investigation.

Genetic variation in leptin and leptin receptor genes as a risk factor for idiopathic male infertility.

The aim of this study was to examine whether there is an association among genetic variability in leptin (LEP) and leptin receptor (LEPR) genes and male infertility. We performed a case-control study and were searching for an association between polymorphisms of LEP and LEPR genes and male infertility. The study group consisted of 317 patients with idiopathic infertility and a control group of 241 fertile men from Slovenia. Four single nucleotide polymorphisms (SNPs) in LEP gene and four single nucleotide polymorphisms (SNPs) in LEPR gene were chosen and genotyped. Statistically significant SNP was further validated in additional 255 infertile patients and 168 controls from Serbia and Macedonia. In the Slovenian population, we found a statistically significant difference in genotype distribution for rs10244329 polymorphism in LEP gene (recessive genotype model, p value=0.048). The trend toward statistically significant difference in genotype distribution for rs10244329 polymorphism was confirmed in the Serbian and Macedonian populations (p value=0.07). Our data suggest that genetic variability in the LEP gene might be associated with male infertility warranting further confirmation and mechanistic investigations.

Association between leptin receptor gene polymorphism and quality of both meat and back fat in large white pigs of ukrainian breeding

Leptin receptor is one of the components of the system of regulating energy homeostasis of the organism. Leptin receptor gene (LEPR) polymorphism is associated with pig carcass index of the content of intramus- cular fat in its valuable parts, which is particularly important when assessing the quality of their carcasses for processing. Intramuscular fat is associated with meat fl avor characteristics and partly determines its tenderness, juiciness, and other parameters. Aim. To analyze LEPR gene (SNP NM001024587.1, p. 1987 C > T) polymor- phism in populations of various pig breeds and to establish its relationship with the quality of both meat and fat of pigs of Large White breed of Ukrainian breeding. Methods. Genetic-population analysis of nine pig breeds, associative analysis on the search connection of LEPR gene polymorphism with quality of both meat and fat of pigs of Large White breed of Ukrainian breeding. LEPR locus genotyping was performed by High Resolution Melting (HRM). Results. All the studied breeds are characterized by polymorphism of the leptin receptor gene (SNP NM001024587.1, p. 1987 C > T), signifi cant breed specifi city in the distribution of frequencies of alleles was established. Statistically confi rmed effect (p < 0.05) of genotypes LEPR on the content of intramuscular fat, total dry matter and moisture in the meat, as well as the moisture content in the back fat of pigs of Ukrainian Large White breed was revealed. Higher content of intramuscular fat was found in the animals with genotype TT, while a smaller amount of intramuscular fat and more moisture in fat was revealed in heterozygotes. Conclusions. Genetic marker LEPR SNP NM001024587.1, p. 1987 C > T can be used in the marker-assisted selection to predict and improve the performance quality of the meat of pigs of Large White breed of the Ukrainian breeding. These results suggest that porcine leptin receptor gene controls the quality of fat comp- lex – inside muscles and in the dorsal part of the carcass.

Associations of TNF-α and IL-6 polymorphisms with osteoporosis through joint effects and interactions with LEPR gene in Taiwan: Taichung Community Health Study for Elders (TCHS-E).

Osteoporosis (OST) is a complex multifactorial disease considered to result from interactions of multiple gene and environmental factors. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 are pleiotropic cytokines essential for bone remodeling; and hormone leptin has immunomodulatory effects that stimulate the synthesis of IL-6 and TNF-α. Leptin is involved in the modulation of bone growth and turnover; and its actions are bound by leptin receptor (LEPR). Prior studies evaluated the effects of TNF-α, IL-6, and LEPR gene polymorphisms separately on bone mineral densities (BMD) or OST. In this study, we assessed the roles of TNF-α and IL-6 gene polymorphisms in OST through joint effects and interactions with LEPR gene. We also evaluated possible joint effects and interactions between these polymorphisms and physical activity. Ten tag-SNPs (rs1799964, rs1800629, rs3093662 in TNF-α; rs1880243, rs1800796, rs1554606 in IL-6; and rs1751492, rs8179183, rs1805096, rs1892534 in LEPR) were used to genotype 103 OST cases and 369 controls. BMD of lumbar spine (LS), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry. Our data showed that TNF-α and IL-6 polymorphisms were associated with overall and site-specific OST in both sexes, and that these associations were dependent on rs1805096 and rs1892534 genotypes of LEPR. In men, LEPR A-G-G-G haplotype was associated with FN OST (OR 4.65, 95% CI 1.61-13.40, p=0.004). Genotype AA/AG of LEPR rs1751492 was associated with overall and FN OST in women without physical activity, but not in women with physical activity (p<0.05 for interaction between physical activity and LEPR rs1751492). In men, we detected significant interactions of IL-6 rs1800796 with LEPR rs1805096 and rs1892534 for FN and TH OST (all p<0.05). Our data indicate that LEPR gene may play joint and interactive roles with TNF-α and IL-6 genes and physical inactivity in development of OST. Haplotype analyses revealed that the correlations tended to be prominent in men with FN OST.

Leptin Receptor Gene Polymorphisms and the Risk of Non-Alcoholic Fatty Liver Disease and Coronary Atherosclerosis in the Chinese Han Population.

BackgroundLeptin receptor (LEPR) polymorphisms have been reported to be associated with lipid metabolism and insulin resistance in various populations. However, whether LEPR polymorphisms are associated with the risks of non-alcoholic fatty liver disease (NAFLD) and coronary atherosclerosis in the Chinese Han population remains unknown.ObjectivesTo investigate the association of LEPR polymorphisms at Q223R and K109R with the risks of NAFLD and coronary atherosclerosis in the Chinese Han population.Patients and MethodsGenotypes of LEPR Q223R and K109R were determined by polymerase chain reaction followed by sequencing in patients with NAFLD (n = 554), coronary atherosclerosis (n = 421), and healthy controls (n = 550). Serum lipid profiles were determined using biochemical methods. Pearson’s χ2 test was used to check for Hardy-Weinberg equilibrium and to analyze the distributions of genotypes’ alleles between groups. Baseline characteristics were analyzed using student’s t-test, paired-samples t-test, or the χ2 test where appropriate.ResultsThe LEPR Q223R A allele significantly reduced the risks of both NAFLD and coronary atherosclerosis (OR = 0.683, 95% CI: 0.527 - 0.884, P = 0.004 and OR = 0.724, 95% CI: 0.548 - 0.955, P = 0.022, respectively). Compared to controls, no significant differences in the genotype and allele frequencies of K109R were found in the NAFLD and coronary atherosclerosis populations, respectively. However, there was a significantly increased risk of coronary atherosclerosis in NAFLD patients who carried the K109R A allele (OR = 2.283, 95% CI: 1.556 - 3.348, P < 0.001).ConclusionsLEPR Q223R polymorphisms may confer a significant risk of NAFLD and coronary atherosclerosis. The A allele in the K109R polymorphism might be considered an independent risk factor for coronary atherosclerosis in NAFLD patients.

Polymorphism in Leptin and Leptin Receptor Genes May Modify Leptin Levels and Represent Risk Factors for Multiple Sclerosis

ABSTRACTBackground: Leptin, the product of the ob gene, can modulate the immune responses and also seems to regulate Th1/Th2 balance by promoting a shift from the Th2 to the Th1 inflammatory cytokine pathway. Therefore, in this study, we aimed to investigate the association between polymorphisms of leptin gene (LEP) and leptin receptor gene (LEPR) and susceptibility to multiple sclerosis (MS). In addition, we investigated the influence of these two common polymorphisms on plasma levels of leptin.Methods: This case–control study was conducted on 232 MS patients and 204 control subjects. Serum level measurement of leptin was performed using enzyme-linked immunosorbent assay (ELISA). G-2548-A LEP polymorphism and 223A/G polymorphism of the LEPR were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results: There was a significant difference in allele/genotype frequencies of LEP gene among MS patients and control subjects (p<0.01). The genotype frequencies of LEPR polymorphism were also significantly different between control subjects and MS patients (p=0.02). The mean serum level of leptin was significantly higher in MS patients as compared with the controls (p<0.01).Conclusion: Our study implicates a significant role of LEP and LEPR polymorphisms and also leptin levels in the risk of MS and its severity. Furthermore, our findings suggest LEP and LEPR polymorphisms as important predictors for increased serum leptin in Iranian MS patients. Although this study provides new clinically relevant information regarding genetic determinants modulating risk of MS, further investigations are necessary to understand better the mechanistic implications of these observations in the development of MS.

Relationships between plasma leptin levels, leptin G2548A, leptin receptor Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population.

The purposes of this study were to examine concentrations of leptin and biochemical parameters in gestational diabetes mellitus (GDM) patients and normal glucose tolerance (NGT) individuals, and also to explore the links of leptin (LEP) G2548A and leptin receptor (LEPR) Gln223Arg polymorphisms with leptin levels and GDM risk among Chinese. Our study included 357 GDM and 355 NGT individuals who were at 24~30 gestational weeks. Plasma leptin and insulin levels were analyzed by ELISA. Gene polymorphisms were genotyped using TaqMan real-time polymerase chain reaction assay. The results showed that plasma leptin levels were significantly higher in the impaired fasting glucose (IFG) group than NGT group (34.35 (26.54, 56.48) ng/mL vs 26.31 (17.99, 37.87) ng/mL, P < 0.05). Plasma leptin levels correlated with plasma fasting insulin levels, pre-pregnant body mass index, homeostasis model assessment-insulin resistance and quantitative insulin sensitivity check index both in GDM and NGT group (P < 0.05). However, neither LEP G2548A nor LEPR Gln223Arg polymorphisms were significantly associated with GDM risk and plasma leptin levels (P > 0.05). Our findings showed that high leptin level was associated with GDM. And larger and more rigorous researches were needed to further explore the association of LEP and LEPR gene polymorphisms and GDM among Chinese population.

Leptin receptor gene polymorphisms and morbid obesity in Mexican patients.

BackgroundHuman obesity is due to a complex interaction among environmental, behavioral, developmental and genetic factors, including the interaction of leptin (LEP) and leptin receptor (LEPR). Several LEPR mutations and polymorphisms have been described in patients with early onset severe obesity and hyperphagic eating behavior; however, some contradictory findings have also been reported. In the present study we explored the association of six LEPR gene polymorphisms in patients with morbid obesity.FindingsTwenty eight patients with morbid obesity and 56 non-obese Mexican Mestizo individuals were included. Typing of rs1137100, rs1137101, rs1805134, Ser492Thr, rs1805094 and rs1805096 LEPR polymorphisms was performed by PCR and allele specific hybridization. The LEPR Ser492Thr polymorphism was monomorphic with the presence of only the Ser492Thr-G allele. Allele C and genotype T/C for rs1805134 polymorphism were associated with susceptibility to morbid obesity (p = 0.02 and p = 0.03, respectively). No association was observed with any haplotype. Linkage disequilibrium (LD) showed that five polymorphisms (rs1137100, rs1137101, rs1805134, rs1805094 and rs1805096) were in absolute (D’ = 1) but none in perfect (r2 = 1) LD.ConclusionsOur results suggest that rs1805134 polymorphism could be involved in the development of morbid obesity, whilst none of the alleles of the LEPR gene, rs1137100, rs1137101, rs1805094 and rs1805096 were associated as risk factors. However, more studies are necessary to confirm or reject this hypothesis.

Polymorphism in leptin receptor gene was associated with obesity in Yogyakarta, Indonesia

BackgroundLeptin is a hormone that regulates homeostasis energy through the central–peripheral mechanism as well as regulates hunger and satiety. Leptin receptor is important in leptin signal transduction that is located mainly in the hypothalamus. The mutation in leptin receptor (LEPR) gene causes splicing abnormality that resulted in truncated receptor, aberrant signal transduction, leptin resistance, and obesity.This study aims to determine the association of LEPR gene polymorphisms, rs1137100 and rs1137101, on phenotype and leptin level between obese and control groups in Yogyakarta population. MethodsWe examined two polymorphisms of LEPR gene, rs1137100 (K109R) and rs1137101 (Q223R) in 110 subjects consisting of 55 obese and 55 healthy adult subjects as controls from Yogyakarta. A correlation study was done between body mass index (BMI), waist and hip circumference, waist to hip ratio (WHR), and leptin level with their genotypes. Statistical analysis was performed using t-test to show the significant difference between the groups. SNPs of LEPR gene for obese and control groups were compared using chi-square analysis. ResultsBody mass index, waist circumference and leptin level in obese group were significantly higher than those in the control group. The frequency of R103R homozygote in obese group was higher than in the control group, whereas Q223Q homozygote in obese group was lower than in the control group. Polymorphism of rs1137100 (K109R) and rs1137101 (Q223R) were associated with obesity and leptin level. ConclusionIn Yogyakarta population, polymorphisms of rs1137100 (K109R) and rs1137101 (Q223R) LEPR gene are associated with obesity. Thus further study on another Indonesian ethnic population is required to investigate the variation in LEPR gene.

Effects of a High Protein/Low Carbohydrate Versus a Standard Hypocaloric Diet on Weight and Cardiovascular Risk Factors, Role of a Lys656asn Polymorphism of Leptin Receptor Gene

Background: The SNP of the leptin receptor (Lys656Asn) has been related with metabolic parameters. The aim of our design was to evaluate the influence of Lys656Asn variant of Leptin receptor gene on weight loss and metabolic parameters secondary to a high protein/low carbohydrate vs. a standard hypocaloric diets. Design: A total of 280 obese subjects were randomly allocated to one of two diets during 9 months (Diet HP (high protein-low carbohydrate hypocaloric diet) and Diet S (standard protein hypocaloric diet)). Results: After both diets and in both genotypes, body mass index (BMI), fat mass, weight, systolic blood pressure and waist circumference decreased, without differences between both diets. With the diet type HP and in both genotypes, triglycerides decreased. In subjects with Lys656Lys genotype, glucose, insulin levels, HOMA-R, total cholesterol and LDL- total cholesterol decreased after HP diet. No statistical changes were detected in Asn allele carriers. After diet S and in patients with Lys656Lys genotypes, only total cholesterol, triglycerides and LDL- total cholesterol decreased, without changes in Asn allele carriers. Conclusion: Obese subjects with Asn656 allele have a different metabolic response than Lys656Lys genotype subjects, secondary to the same weight loss with two different hypocaloric diets.

Association between Leptin G2548A and Leptin Receptor Q223R Polymorphisms with Type 2 Diabetes in an Iranian Population.

The leptin (LEP G2548A) and leptin receptor (LEPR Q223R) gene polymorphisms have been variably associated with type 2 diabetes (T2D) in different populations. In this study we hypothesized that these variants might be associated with T2D and related metabolic traits in an Iranian population. The LEP G2548A and LEPR Q223R genotypes were determined by PCR-RFLP in 378 normoglycemic controls and 154 T2D patients. Bonferroni correction was applied for the correction of multiple testing. The A allele of the LEP G2548A polymorphism was more prevalent in females of the T2D group than the controls (p = 0.009). In a recessive model (GG+GA vs. AA), the frequency of the AA genotype was higher in female patients compared to normoglycemic subjects 134.9% vs. 19.3%, OR 2.60 (1.27-5.31), p = 0.0091. Multivariate logistic regression analysis also showed that the AA genotype of the LEP G2548A polymorphism is an independent risk factor for T2D in females. No significant association was found between the allele and genotype frequencies of the LEPR Q223R variant with T2D in female and male groups. In addition, no significant difference in anthropometrical and biochemical parameters was observed between the genotypes of LEP and LEPR variants in gender-specific groups in both non-diabetic and diabetic subjects. Our results suggest that the LEP G2548A polymorphisms might associate with T2D among Iranian female subjects, whereas the LEPR Q223R variant is not associated with T2D and its related metabolic traits in this population.

Lack of association variants of leptin and leptin receptor gene and OSAHS in Chinese Han population

Associations of polymorphisms leptin, leptin receptor (LEPR) gene and obstructive sleep apnea hypopnea syndrome (OSAHS) had been explored in other country, and conflicting conclusions were drawn from different racial. However, relevant reports were scarce in China, therefore, we conducted the research to testify the hypothesis whether both single nucleotide polymorphisms (SNPs) of the leptin and LEPR gene were susceptive marker for OSAHS in Chinese Han people. 130 OSAHS patients and 136 health controls with matched age and gender were recruited into the study for genotyping of rs4731426, rs11763517, rs10954173, rs2071045, and rs11761556 in leptin gene and rs1137101 in LEPR gene. Association of these SNPs and OSAHS risk was estimated by computing the odds ratio and 95 % confidence interval from multivariate unconditional logistic regression analyses with adjustment for gender and age. The experimental results indicated that frequency of the haplotypes rs4731426, rs11763517, rs10954173, rs2071045, and rs11761556 of leptin and rs1137101 in LEPR locus had no significant differences between controls and cases. Though we further stratified analysis based on gender, weight and severity of disease, no difference was observed among subgroups. The research demonstrated that polymorphisms of leptin and LEPR gene were not major contributors to OSAHS susceptibility in Chinese Han population.

Polymorphism of rs2767485 in Leptin Receptor Gene is Associated With the Occurrence of Adolescent Idiopathic Scoliosis.

A genetic association study of leptin receptor (LEPR) gene with adolescent idiopathic scoliosis (AIS) in the Chinese Han population. To determine whether LEPR gene polymorphisms are associated with the predisposition and/or disease severity of AIS. Patients with AIS were reported to have lower body mass index (BMI), abnormal leptin bioavailability, and systemic lower bone mass, which implied that leptin/LEPR signaling pathway may be implicated in the etiology of AIS. Previous association study of the polymorphisms in leptin gene did not show significant differences between AIS cases and controls. However, no study has been done to investigate the relationship between genetic polymorphisms of the LEPR gene and susceptibility to AIS. 570 patients with AIS aged 10 to 18 years were enrolled, and 570 age-matched healthy subjects were recruited as controls. 6 single nucleotide polymorphisms (SNPs) (rs1137101, rs1137100, rs4655555, rs2767485, rs1751492, and rs8179183) of LEPR gene were selected. The polymorphisms were genotyped using the polymerase chain reaction (PCR)-based Invader assay. Case-control study was performed to define the contribution of the 6 SNPs to predisposition of AIS. 1-way analysis of variance (ANOVA) test was used to compare the mean Cobb angles and BMI among patients with different genotypes in case-only analyses. Statistical significance was set at P < 0.05. Both the genotype and allele frequencies of SNP rs2767485 were significantly different between the patient with AIS and the control groups. No significant difference of allele frequency was noted in other 5 SNPs between the patients with AIS and the normal controls. Both the mean maximum Cobb angles and BMI of different genotype AIS groups were similar to each other for all the 6 SNPs (P > 0.05). Polymorphism of rs2767485 in LEPR gene is associated with the occurrence of AIS, suggesting LEPR is a predisposition gene.

Association of Leptin Receptor Gene Polymorphisms with Genetic Susceptibility to Ischemic Stroke

Ischemic stroke is a multifactorial disease that is influenced by both genetic and environmental factors. Identification of the genetic factors that are underlining this disease is important. Leptin receptor (LEPR) mediates the leptin-regulated human energy homeostasis, and mutations of LEPR can increase cardiovascular risks and may predispose an individual to ischemic stroke. We analyzed distribution of 3 single nucleotide polymorphisms (SNPs) of LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) in 101 patients with ischemic stroke and 105 controls by polymerase chain reaction-restriction fragment length polymorphism strategy. Our results showed that there were significant differences in the genotype and allele distribution of Lys109Arg and Gln223Arg polymorphisms of the LEPR gene between case and control. The 109GG and 223GG genotype were associated with a significantly increased risk of ischemic stroke (odds ratio [OR], 3.23; P = .001 and OR, 2.87; P = .008, respectively). The 109G and 223G alleles carriers were correlated with an increased incidence of ischemic stroke (OR, 2.72; P = .001; OR, 2.94; P = .004). By haplotype analyses, we found that 109A/223G/656G haplotype was associated with an increased risk of ischemic stroke although this was not observed in the control group (OR, 3.86; P = .029). LEPR 109GG and 223GG genotypes and the 109G and 223G alleles are associated with the risk of ischemic stroke. Our data suggest that LEPR Lys109Arg and Gln223Arg polymorphisms could be used as genetic predictive factor for ischemic stroke.

Leptin Receptor Gene Polymorphism May Hamper Results Of Aerobic Plus Resistance Training Among Obese Adolescents

BACKGROUND: Obesity has reached epidemic proportions globally, where leptin plays an important role. Although obesity is associated with metabolic alterations and increased cardiovascular risk, not all obese subjects have these abnormalities. Indeed, not everyone respond in the same way to obesity treatment, which could be partly explained by genetic variations. AIM: To investigate the influence of single nucleotide polymorphisms in the leptin receptor gene LEPR (rs2767485) in the response of long term (1 year) aerobic plus resistance training associated with lifestyle therapy among obese Brazilian adolescents. METHODS: A total of 57 of obese adolescents were enrolled in one year of weight loss therapy (exercise training plus clinical, nutritional and psychological counselling). Blood samples were collected to analyse metabolic, adipokines, neuropeptides parameters and LEPR genotyping. Visceral fat was measured by ultrasound and body composition was measured by pletismography. Adolescents were grouped according to genotype (TT or CT+CC group). The effect of the therapy was analysed through ANOVA and Wilcox, according to normality. Difference between groups was determined by student t-test. Pearson correlation and logistic regression were performed, with value set at < 0.05. RESULTS: Genotyping CT +CC group presented higher values of VLDL-c, triglycerides and MCP-1 levels when compared with wild type group (TT), at baseline. Aerobic plus resistance training associated to life style therapy were effective to improve body composition in both genotypes. The TT group did not present alterations lipid profile at baseline and was the only group who was able to improve LDL-cholesterol. In addition, the hiperleptinemia state was reversed in this group. Although, CT + CC improved cholesterol and triglycerides, these adolescents kept in the hiperleptinemia state. In agreement, CT + CC group increased AGRP values and in the logistic model it seems to be an independent factor. CONCLUSION: Genetic variation on Leptin receptor gene (rs2767485) might increases the chances of developing cardiovascular disease in obese adolescents by increasing triglycerides, VLDL-c and MCP-1 levels. Data suggest that CT+ CC genotype present more difficulty to normalize neuroendocrine pathway and hiperleptinemia state.

Leptin and leptin receptor gene polymorphisms are associated with clinical and metabolic parameters in resistant hypertension

The interest in perivascular cells as a niche for adult hematopoietic stem cells (HSCs) is significantly growing. In the adult bone marrow (BM), perivascular cells and HSCs cohabit. Among perivascular cells, pericytes are precursors of mesenchymal stem/stromal cells (MSCs) that are capable of differentiating into osteoblasts, adipocytes and chondrocytes. In situ, pericytes are recognised by their localisation to the abluminal side of the blood vessel wall and closely associated with endothelial cells, in combination with the expression of markers such as CD146, neural glial 2 (NG2), platelet derived growth factor receptor β (PDGFRβ), α-smooth muscle actin (α-SMA), nestin (Nes) and/or leptin receptor (LepR). However, not all pericytes share a common phenotype: different immunophenotypes can be associated with distinct mesenchymal features, including hematopoietic support. In adult BM, arteriolar and sinusoidal pericytes control HSC behaviour, maintenance, quiescence and trafficking through paracrine effects. Different groups identified and characterized hematopoietic supportive pericyte subpopulations using various markers and mouse models. In this review, we summarize recent work performed by others to understand the role of the perivascular niche in the biology of HSCs in adults, as well as their importance in the development of therapies.

Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid.

Background:Weight gain is the most frequent adverse effect of valproic acid (VPA) treatment, resulting in poor compliance and many endocrine disturbances. Similarities in the weight change of monozygotic twins receiving VPA strongly suggests that genetic factors are involved in this effect. However, few studies have been conducted to identify the relevant genetic polymorphisms. Additionally, the causal relationship between the VPA concentration and weight gain has been controversial. Thus, we investigated the effects of single nucleotide polymorphisms (SNPs) in several appetite stimulation and energy homeostasis genes and the steady state plasma concentrations (Css) of VPA on the occurrence of weight gain in patients.Methods:A total of 212 epilepsy patients receiving VPA were enrolled. Nineteen SNPs in 11 genes were detected using the Sequenom MassArray iPlex platform, and VPA Css was determined by high-performance liquid chromatography (HPLC).Results:After 6 months of treatment, 20.28% of patients were found to gain a significant amount of weight (weight gained ≥7%). Three SNPs in the leptin receptor (LEPR), ankyrin repeat kinase domain containing 1 (ANKK1), and α catalytic subunit of adenosine monophosphate-activated protein kinase (AMPK) showed significant associations with VPA-induced weight gain (p < 0.001, p = 0.017 and p = 0.020, respectively). After Bonferroni correction for multiple tests, the genotypic association of LEPR rs1137101, the allelic association of LEPR rs1137101, and ANKK1 rs1800497 with weight gain remained significant. However, the VPA Css in patents who gained weight were not significantly different from those who did not gain weight (p = 0.121).Conclusions: LEPR and ANKK1 genetic polymorphisms may have value in predicting VPA-induced weight gain.

Leptin and leptin receptor gene polymorphisms are correlated with production performance in the Arctic fox.

The polymerase chain reaction-single-strand conformation polymorphism technique was employed to measure mononucleotide diversity in the coding region of the leptin and leptin receptor genes in the Arctic fox. The relationships between specific genetic mutations and reproductive performance in Arctic foxes were determined to im-prove breeding strategies. We found that a leptin gene polymorphism was significantly associated with body weight (P < 0.01), abdominal circumference (P < 0.01), and fur length (P < 0.01). Furthermore, a polymorphism in the leptin receptor gene was associated with carcass weight and guard hair length (P < 0.01). Leptin and leptin receptor gene combinatorial genotypes were significantly associated with abdominal circumference, fur length (P < 0.01), and body weight (P < 0.05). The leptin gene is thus a key gene affecting body weight, abdominal circumference, and fur length in Arctic foxes, whereas variations in the leptin receptor mainly affect carcass weight and guard hair. The marker loci identified in this study can be used to assist in the selection of Arctic foxes for breeding to raise the production performance of this species.

Serum Leptin Levels, Leptin Receptor Gene (LEPR) Polymorphism, and the Risk of Systemic Lupus Erythematosus in Kashmiri Population

The study is conducted to evaluate relationship between LEPRQ223R (Gln > Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG + GG) in cases compared to controls [OR = 2.52, CI = 1.18–5.35, p = 0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR = 1.49, p = 0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR = 11.8, CI = 1.6–85.1, p = 0.002] and an inverse association with cardiac disorder [OR = 0.09, CI = 0.02–0.46, p = 0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9 ± 19.5 vs 14.8 ± 10.4, p < 0.001). SLE patients in the highest quartile leptin levels (≥32.5 ng/mL) were significantly more likely to have higher BMI (p = 0.001) and increased risk of developing arthritis (p = 0.02). Furthermore positive association was observed between the variant genotype(AG + GG) and leptin levels (p = 0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.

Effect of Lys656Asn Polymorphism of Leptin Receptor Gene on Cardiovascular Risk Factors and Serum Adipokine Levels after a High Polyunsaturated Fat Diet in Obese Patients.

Human obesity is characterized by high levels of leptin, and leptin levels may change with weight loss and dietary restriction. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on cardiovascular risk factors, weight loss, and serum leptin levels to a high polyunsaturated fatty acid (PUFA) hypocaloric diet in obese patients. A sample of 132 obese patients was analyzed in a prospective way with a dietary intervention. The enriched PUFAs hypocaloric intervention consisted in a diet of 1,459 kcal, 45.7% of carbohydrates, 34.4% of lipids, and 19.9% of proteins. In wild-type group, BMI (-1.9 ± 1.4 kg/m(2) ), weight (-4.4 ± 3.2 kg), fat mass (-4.2 ± 3.8 kg), waist circumference (-4.1 ± 3.1 cm), systolic blood pressure (-7.0 ± 12.1 mmHg), diastolic blood pressure (-3.9 ± 6.8 mmHg), insulin (-1.8 ± 5.6 MUI/l) and HOMA-IR (-0.5 ± 1.5 Units) decreased. In mutant genotype group, BMI (-2.0 ± 2.1 kg/m(2) ), weight (-3.6 ± 4.1 kg), waist circumference (-3.1 ± 4.1 cm), total cholesterol (-25.2 ± 19.6 mg/dl), LDL cholesterol (-16.6 ± 25.6 mg/dl), and tryglicerides (-26.6 ± 39.1 mg/dl) decreased. Only leptin levels have a significant decrease in wild genotype group (-6.6 ± 10.2 ng/ml) (25.1%). Carriers of ASn656 allele have a different response than wild-type obese, with a lack of decrease in insulin levels, leptin levels, and HOMA-IR. However, obese patients with this mutant allele have a better lipid profile after weight loss.