Single Nucleotide Polymorphisms In LEPR Research Articles

Association between thermogenic brown fat and genes under positive natural selection in circumpolar populations

BackgroundAdaptation to cold was essential for human migration across Eurasia. Non-shivering thermogenesis through brown adipose tissue (BAT) participates in cold adaptation because some genes involved in the differentiation and function of BAT exhibit signatures of positive natural selection in populations at high latitudes. Whether these genes are associated with the inter-individual variability in BAT thermogenesis remains unclear. In this study, we evaluated the potential associations between BAT activity and single nucleotide polymorphisms (SNPs) in candidate gene regions in East Asian populations.MethodsBAT activity induced by mild cold exposure was measured in 399 healthy Japanese men and women using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). The capacity for cold-induced thermogenesis and fat oxidation was measured in 56 men. Association analyses with physiological traits were performed for 11 SNPs at six loci (LEPR, ANGPTL8, PLA2G2A, PLIN1, TBX15-WARS2, and FADS1) reported to be under positive natural selection. Associations found in the FDG-PET/CT population were further validated in 84 healthy East Asian men and women, in whom BAT activity was measured using infrared thermography. Associations between the SNP genotypes and BAT activity or other related traits were tested using multiple logistic and linear regression models.ResultsOf the 11 putative adaptive alleles of the six genes, two intronic SNPs in LEPR (rs1022981 and rs12405556) tended to be associated with higher BAT activity. However, these did not survive multiple test comparisons. Associations with lower body fat percentage, plasma triglyceride, insulin, and HOMA-IR levels were observed in the FDG-PET/CT population (P < 0.05). Other loci, including TBX15-WARS2, which is speculated to mediate cold adaptation in Greenland Inuits, did not show significant differences in BAT thermogenesis.ConclusionsOur results suggest a marginal but significant association between LEPR SNPs. However, robust supporting evidence was not established for the involvement of other loci under positive natural selection in cold adaptation through BAT thermogenesis in East Asian adults. Given the pleiotropic function of these genes, factors other than cold adaptation through BAT thermogenesis, such as diet adaptation, may contribute to positive natural selection at these loci.

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.

Association of Single Nucleotide Polymorphisms in LEP, LEPR, and PPARG With Humoral Immune Response to Influenza Vaccine.

Background: Although previous studies have proposed leptin plays an important role in energy metabolism as well as in immune response, the effects of leptin-related genes on influenza vaccine-induced immune response remain unexplored. In this study, we aimed to investigate the potential association of leptin gene (LEP), leptin receptor gene (LEPR), and peroxisome proliferator activated receptor gamma gene (PPARG) polymorphisms with humoral immune response to influenza vaccine. Methods: Based on the seroconversion to influenza vaccine, 227 low-responders and 365 responders were selected in this study, and 11 candidate single nucleotide polymorphisms (SNPs) were genotyped using the MassARRAY technology platform. Univariate and multivariate logistic regression analyses were used to explore the association of SNPs in LEP, LEPR, and PPARG with humoral immune response to influenza vaccine. We also conducted a stratified analysis by gender to further clarify this association. The haplotypes analysis was performed using SNPStats. Results: Significant differences were observed in the genotypic distribution of PPARG rs17793951 between the two groups (p = 0.001), and the PPARG rs17793951 AG + GG genotype was associated with a higher risk of low responsiveness to influenza vaccine adjusted for gender and age (additive genetic model: OR = 2.94, 95% CI = 1.67–5.19, dominant genetic model: OR = 2.81, 95% CI = 1.61–4.92). No significant association of other SNPs in LEP and LEPR with immune response to influenza vaccine was found. The stratified analysis found the gender difference in the association of LEPR and PPARG variants with immune response to influenza vaccine. We found that LEPR rs6673591 GA + AA genotype was correlated with low responsiveness to influenza vaccine only in males (OR = 1.96, 95% CI = 1.05–3.67), and PPARG rs17793951 AG + GG genotype was associated with low responsiveness to influenza vaccine in females (OR = 3.28, 95% CI = 1.61–6.67). Compared with the CGGAGGC haplotype composed of LEPR rs1327118, rs7602, rs1137101, rs1938489, rs6673591, rs1137100, and rs13306523, the CAAAAAC haplotype was positively correlated with immune response of influenza vaccine (OR = 0.34, 95% CI = 0.15–0.77). Haplotype TG comprised of PPARG rs796313 and rs17793951 was associated with a 2.85-fold increased risk of low responsiveness to influenza vaccine. Conclusion: Our study identified that PPARG rs17793951 variants were significantly associated with the immune response to influenza vaccine.

Obesity in Children with Leptin Receptor Gene Polymorphisms.

The study of single nucleotide polymorphisms (SNPs) of the leptin receptor gene (LEPR) based on next generation genomic sequencing (NGS) data is becoming an increasingly important aspect of diagnosis, treatment and prevention of both metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) phenotypes. 35 obese children 6-18 years old were examined by the NGS method with bioinformatic analysis. The main group (n = 18) was formed by children with MUO, according to the recommendations of the expert group of the National Heart, Lung, and Blood Institute. The control group (n = 17) was represented by children with MHO. Statistical methods were used: analysis of variance, Wald's sequential analysis, Spearman's correlation analysis, analysis of nominal data and multiple discriminant analysis. 10 types of non-synonymous SNPs (rs3790435, rs1137100, rs2186248, rs70940803, rs79639154, rs1359482195, rs1137101, rs1805094, rs13306520, rs13306522) of the LEPR gene in obese children have been identified. Multiple discriminant analysis demonstrated that the following LEPR SNPs are of greatest importance in the development of MUO: rs3790435, rs13306522, rs13306520. Analysis of nominal data revealed significant differences in the groups for Copy number variation (CNV) rs3790435 of the LEPR gene. Wald's analysis allowed us to identify 6 important predictors of MUO (І ≥ 0.5): 2 CNV rs3790435 (Relative Risk, RR = 2, Prognostic coefficient, PC = +2.76); male gender of the child (RR = 1.3, PC = +1.35); rs3790435 (RR = 1.9, PC = +2.76); hyperleptinemia more than 40.56 ng/ml (RR = 2, PC = +3); CNV rs1359482195 ≥ 3 (RR = 1.9, PC = +5.8); SNP of the LEPR gene ≥4 (RR = 3.8, PC = +5.8). Children with the genotype rs3790435 gene LEPR had signs of MUO more often.

Characterization of genetic and phenotypic heterogeneity of obstructive sleep apnea using electronic health records

BackgroundObstructive sleep apnea (OSA) is defined by frequent episodes of reduced or complete cessation of airflow during sleep and is linked to negative health outcomes. Understanding the genetic factors influencing expression of OSA may lead to new treatment strategies. Electronic health records (EHRs) can be leveraged to both validate previously reported OSA-associated genomic variation and detect novel relationships between these variants and comorbidities.MethodsWe identified candidate single nucleotide polymorphisms (SNPs) via systematic literature review of existing research. Using datasets available at Geisinger (n = 39,407) and Vanderbilt University Medical Center (n = 24,084), we evaluated associations between 40 previously implicated SNPs and OSA diagnosis, defined using clinical codes. We also evaluated associations between these SNPs and OSA severity measures obtained from sleep reports at Geisinger (n = 6571). Finally, we used a phenome-wide association study approach to help reveal pleiotropic genetic effects between OSA candidate SNPs and other clinical codes and laboratory values available in the EHR.ResultsMost previously reported OSA candidate SNPs showed minimal to no evidence for associations with OSA diagnosis or severity in the EHR-derived datasets. Three SNPs in LEPR, MMP-9, and GABBR1 validated for an association with OSA diagnosis in European Americans; the SNP in GABBR1 was associated following meta-analysis of results from both clinical populations. The GABBR1 and LEPR SNPs, and one additional SNP, were associated with OSA severity measures in European Americans from Geisinger. Three additional candidate OSA SNPs were not associated with OSA-related traits but instead with hyperlipidemia and autoimmune diseases of the thyroid.ConclusionsTo our knowledge, this is one of the largest candidate gene studies and one of the first phenome-wide association studies of OSA genomic variation. Results validate genetic associates with OSA in the LEPR, MMP-9 and GABBR1 genes, but suggest that the majority of previously identified genetic associations with OSA may be false positives. Phenome-wide analyses provide evidence of mediated pleiotropy. Future well-powered genome-wide association analyses of OSA risk and severity across populations with diverse ancestral backgrounds are needed. The comprehensive nature of the analyses represents a platform for informing future work focused on understanding how genetic data can be useful to informing treatment of OSA and related comorbidities.

Association study of candidate genes with obesity and metabolic traits in antipsychotic-treated patients with first-episode psychosis over a 2-year period.

Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with second-generation APs, is strongly linked to weight gain, which increases patients' risk of developing obesity and other metabolic diseases. There is an important genetic risk component that can contribute to the appearance of these disturbances. The aim of the present study was to evaluate the effect of polymorphisms in selected candidate genes on obesity and other anthropometric and metabolic traits in 320 AP-treated FEP patients over the course of a 2-year follow-up. These patients were recruited in the multicentre PEPs study (Phenotype-genotype and environmental interaction; Application of a predictive model in first psychotic episodes). A total of 127 validated single nucleotide polymorphisms (SNPs) in 18 candidate genes were included in the genetic analysis. After Bonferroni correction, SNPs in ADRA2A, FTO, CNR1, DRD2, DRD3, LEPR and BDNF were associated with obesity, abdominal circumference, triglycerides, HDL cholesterol, and/or percentage of glycated haemoglobin. Although our results should be interpreted as exploratory, they support previous evidence of the impact of these candidate genes on obesity and metabolic status. Further research is required to gain a better knowledge of the genetic variants that can be considered relevant metabolic risk factors. The ability to identify FEP patients at higher risk for these metabolic disturbances would enable clinicians to better select and control their AP treatment.

Selected Candidate Genes and Obesity Among Ghanaian Adults: A Case-control Study at the Korle-Bu Teaching Hospital (Dietherapy Unit) Accra (P15-014-19)

ObjectivesThe aim of the study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of selected genes (β3-adrenergic receptors-ADRB3, Leptin receptor-LEPR, Peroxisome proliferator activator receptor γ-PPARG) and obesity among Ghanaian adults. MethodsThis was a case-control study comprising 24 cases of newly diagnosed obese; BMI ≥30 kg/m2, at the Dietherapy Unit of the Korle-Bu Teaching Hospital (KBTH), and 32 controls of non-obese staff and clinical students at KBTH. A validated questionnaire was used for demographic, dietary and anthropometric data. Dietary intake was assessed using a food frequency questionnaire, and DNA extracted from mouth rinse water samples. SNPs in the ADRB3, LEPR and PPARG genes were determined by polymerase chain reaction restriction fragment length polymorphism (PCR –RFLP). ResultsThere were statistically significant differences in BMI, WHR and MUAC measurements between cases and controls (all p s˂ 0.0001). There was no statistically significant difference (P = 0.3032) between the mean energy intakes of both cases and controls. DNA fragments for the PPARG gene was amplified in 55 respondents. No relationship was observed between PPARG (Pro12Pro) SNP and BMI, MUAC and WHR among participants. Amplification was successful in 19 cases and 24 controls for ADRB3 (Trp64Trp & Trp64Arg). No significant difference (all ps > 0.05) emerged for the ADRB3 SNPs frequencies between the cases and the controls for BMI, MUAC and WHR. LEPR amplification was successful in 15 cases and 14 controls. Amplicons of six cases, all in the OBClass 1 to OBClass 3 range, indicated the presence of the Gln223Arg SNP after RFLP. A significant difference (all ps < 0.05) emerged for LEPR (Gln223Arg) SNP frequencies between the cases and the controls for BMI, MUAC and WHR. ConclusionsThere were no observed relationships among ADRB3, PPARG SNPs and BMI, MUAC and WHR. LEPR (Gln223Arg) SNP was statistically associated with BMI, MUAC and WHR. Funding Sources1. College of Health Sciences, University of Ghana Research Grant for MSc/MPhil Thesis/Dissertation. 2. Self funding.

Association study between LEPR, MC4R polymorphisms and overweight/obesity in Chinese Han adolescents

ObjectiveObesity is one of the major health problems strongly influenced by lifestyle, genetic and environmental factors. Previous studies have reported many single-nucleotide polymorphisms (SNPs) are associated with obesity in different races. This study aimed to explore the genetic associations between LEPR, MC4R polymorphisms and overweight/obesity in Chinese Han adolescents. Methods400 adolescents including 222 health controls and 178 overweight/obese adolescents were genotyped and their body compositions were also analyzed in this study. ResultsWe found that allelic and genotypic frequencies of LEPR SNP rs8179183 were significantly different between controls and cases (allelic frequency p < 0.001; genotypic frequency p = 0.004). These difference was still significant (allelic frequency p < 0.011; genotypic frequency p = 0.024) after Bonferroni correction. Moreover, we found that rs8179183 was associated with serum triglyceride level after adjusting for age and body mass index (BMI) (p = 0.037). ConclusionIn summary, our results found a significant association between LEPR SNP rs8179183 and overweight/obesity in Chinese Han adolescent. This study may provide a reference for future studies of obesity.

Polymorphisms in Acute Coronary Syndrome

Background: Because of their effects on inflammatory processes, some genes are candidates for association with Acute Coronary Syndrome (ACS). While a relationship between Single Nucleotide Polymorphisms (SNP) and ACS has been suggested in some populations, but not in others, genotype characterization of genes related to inflammatory reactions, becomes necessary for specific populations. Aim: In this study, we evaluate IL6 (rs1800795), LEPR (rs6700896) and IL1b (rs16944) SNPs in a healthy population and compare the frequencies with other populations to characterize them in a region of Brazil and investigate the role of SNPs as prognostic markers in the development of ACS in futures studies. Methods: IL6, LEPR and IL1b genes were genotyped in 295 blood donors from Fundacao de Hematologia e Hemoterapia de Pernambuco. Genotyping was carried out by polymerase chain reaction, followed by DNA sequencing or enzymatic cleavage. G Williams test and odds ratio with confidence intervals of 95% were used. The significance value was p Results: There was no difference in genotype distribution between gender or age groups. Genotypic and allelic frequencies were similar between Brazilian populations but different from most other population’s analyzed (p Conclusions: Genotypic characterization of genes that can influence the development of ACS is important, since it can provide a tool for future studies in the use of genetic markers in prevention and diagnosis of diseases. Keywords : Acute Coronary Syndrome; Blood Donors; Prognostic Markers; Polymerase Chain Reaction; Single Nucleotide Polymorphisms

Relationship between polymorphisms in the CRP, LEP and LEPR genes and high sensitivity C-reactive protein levels in Spanish children.

We investigated the association of single nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP), leptin (LEP) and leptin receptor (LEPR) genes with high sensitivity CRP (hs-CRP) levels in two independent cohorts of healthy Spanish children. We measured hs-CRP levels in 646 6-8-year-old and 707 12-16-year-old children using a high-sensitivity C-Reactive Protein ELISA kit. Four SNPs in the CRP gene (rs1205, rs1130864, rs2794521 and rs1800947), one SNP in the LEP gene (rs7799039) and two SNPs in the LEPR (rs1137100 and rs1137101) gene were determined by TaqMan® allelic discrimination assays. The four CRP SNPs studied were significantly (p<0.05) associated with hs-CRP levels in both cohorts. Furthermore, two common CRP haplotypes (constructed using the SNPs in order: rs1205, rs1130864, rs1800947, rs2794521) ACGA and GCGG were associated with significantly lower CRP levels (p<0.05) at both ages. The LEPR SNPs rs1137100 (K109R) and rs1137101 (Q223R), and LEP SNP rs7799039 (G2548A) were also associated to hs-CRP levels (p<0.05) in both cohorts. hs-CRP levels in healthy Spanish children, besides being associated to common polymorphisms in the CRP gene, are associated to polymorphisms in the LEP and LEPR genes, which suggests that other loci, in addition the CRP gene, may have a role determining CRP levels in children.

Association of the leptin receptor Gln223 Arg polymorphism with lipid profile in obese Pakistani subjects

ObjectiveLeptin receptor gene (LEPR) encodes a receptor for leptin hormone expressed in hypothalamus and single nucleotide polymorphisms in LEPR may have a considerable effect on obesity phenotype. The aim of this study was to investigate an extensively studied LEPR polymorphism Gln223 Arg in a Pakistani study group and its association patterns with different serum biochemical parameters. MethodsThe study included 250 obese and 225 nonobese subjects. Gln223 Arg polymorphism was genotyped by polymerase chain reaction restriction fragment-length polymorphism. Anthropometric parameters and plasma glucose, total cholesterol, triacylglycerols, high density lipoprotein cholesterol, low density lipoprotein cholesterol, leptin, and insulin were measured. ResultsThe Gln223 Arg polymorphism was found to be significantly associated with body mass index, systolic and diastolic blood pressure, and weight only in obese subjects, and with all lipid parameters in both obese and nonobese subjects when Gln/Gln or Gln/Arg genotypes were compared with Arg/Arg genotype. ConclusionsThe LEPR Gln223 is associated with obesity, lipid parameters, and plasma glucose in all subjects, with weight, body mass index, and systolic and diastolic blood pressure only in obese subjects, but showed no association with leptin, insulin, and HOMA-IR in a Pakistani study group.

Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population.

BackgroundThis study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene LEP (A19G and G2548A) and leptin receptor gene LEPR (K109R and Q223R) and their association with fasting plasma leptin level (PLL) and obesity in a Malaysian suburban population in Kampar, Perak.MethodsConvenience sampling was performed with informed consents, and the study sample was drawn from patients who were patrons of the Kampar Health Clinic. A total of 408 subjects (mean age, 52.4 ± 13.7 years; 169 men, 239 women; 190 obese, 218 non-obese; 148 Malays, 177 ethnic Chinese, 83 ethnic Indians) participated. Socio-demographic data and anthropometric measurements were taken, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe LEP A19G, G2548A and LEPR K109R, Q223R variant allele frequencies were 0.74, 0.67 and 0.61, 0.79, respectively. The genotype and allele distributions of these gene variants were significantly different among ethnic groups, but not among body mass index (BMI) classes. Subjects with LEPR K109 and Q223 allele had significantly higher systolic blood pressure and adiposity indices after adjustment for ethnicity (higher BMI, total body and subcutaneous fat; lower skeletal muscle percentage). Subjects with LEPR 109R allele had lower PLL than their wild-type allele counterparts. The influence of LEP A19G and G2548A SNPs on blood pressures, anthropometrics, and PLL was not evident. Interestingly, synergistic effect of the LEP and LEPR SNPs was observed as subjects homozygous for all four SNPs studied exhibited significantly higher subcutaneous fat and PLL than those with other genotype combinations.ConclusionsThe LEP and LEPR SNPs in this study may not be an obesity marker among Malaysians in this population, but were associated with ethnicity. Our findings suggest that each of these SNPs contributes to minor but significant variation in obesity-related traits and in combination they display synergistic effects on subcutaneous fat and PLL.

Family-Based Association Study Between SLC2A1, HK1, and LEPR Polymorphisms With Myelomeningocele in Chile

Obese/diabetic mothers present a higher risk to develop offspring with myelomeningocele (MM), evidence supporting the role of energy homeostasis-related genes in neural tube defects. Using polymerase chain reaction-restriction fragment length polymorphism, we have genotyped SLC2A1, HK1, and LEPR single-nucleotide polymorphisms in 105 Chilean patients with MM and their parents in order to evaluate allele-phenotype associations by means of allele/haplotype transmission test (TDT) and parent-of-origin effects. We detected an undertransmission for the SLC2A1 haplotype T-A (rs710218-rs2229682; P = .040), which was not significant when only lower MM (90% of the cases) was analyzed. In addition, the leptin receptor rs1137100 G allele showed a significant increase in the risk of MM for maternal-derived alleles in the whole sample (2.43-fold; P = .038) and in lower MM (3.20-fold; P = .014). Our results support the role of genes involved in energy homeostasis in the risk of developing MM, thus sustaining the hypothesis of diverse pathways and genetic mechanisms acting in the expression of such birth defect.

Association of single nucleotide polymorphisms (SNPs) in leptin re-ceptor gene with knee osteoarthritis in the Ningxia Hui population

To investigate the association between primary knee osteoarthritis (OA) and single nucleotide polymorphism (SNP) (A668G) of leptin receptor gene (LEPR) in the Ningxia Hui population. A case-control association study has been adopted in this thesis. The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis were performed to investigate the SNP of A668G site within LEPR from 148 patients with knee OA and 155 controls (asymptomatic and radiographically negative) with matched age and gender among Ningxia Hui population. In addition, genotypes of LEPR were verified by direct sequence analysis on PCR products. The result indicates that allele and genotype frequencies (P=0.024 and 0.008, respectively) in LEPR SNP A668G were significantly different in the knee OA patients group and control group, and in the knee OA patients group, the serum levels of leptin decreased significantly (P<0.001) and the serum levels of soluble leptin receptor increased significantly (P<0.001) compared with control group. Therefore, LEPR SNP A668G is associated with susceptibility to knee OA, which would be used as the genetic marker in predicting the risk of knee OA and would be one of the candidate genes in early prevention and control.

SNP analyses of postprandial responses in (an)orexigenic hormones and feelings of hunger reveal long-term physiological adaptations to facilitate homeostasis

The postprandial responses in (an)orexigenic hormones and feelings of hunger are characterized by large inter-individual differences. Food intake regulation was shown earlier to be partly under genetic control. This study aimed to determine whether the postprandial responses in (an)orexigenic hormones and parameters of food intake regulation are associated with single nucleotide polymorphisms (SNPs) in genes encoding for satiety hormones and their receptors. Peptide YY (PYY), glucagon-like peptide 1 and ghrelin levels, as well as feelings of hunger and satiety, were determined pre- and postprandially in 62 women and 41 men (age 31+/-14 years; body mass index 25.0+/-3.1 kg/m(2)). Dietary restraint, disinhibition and perceived hunger were determined using the three-factor eating questionnaire. SNPs were determined in the GHRL, GHSR, LEP, LEPR, PYY, NPY, NPY2R and CART genes. The postprandial response in plasma ghrelin levels was associated with SNPs in PYY (215G>C, P<0.01) and LEPR (326A>G and 688A>G, P<0.01), and in plasma PYY levels with SNPs in GHRL (-501A>C, P<0.05) and GHSR (477G>A, P<0.05). The postprandial response in feelings of hunger was characterized by an SNP-SNP interaction involving SNPs in LEPR and NPY2R (668A>G and 585T>C, P<0.05). Dietary restraint and disinhibition were associated with an SNP in GHSR (477G>A, P<0.05), and perceived hunger with SNPs in GHSR and NPY (477G>A and 204T>C, P<0.05). Part of the inter-individual variability in postprandial responses in (an)orexigenic hormones can be explained by genetic variation. These postprandial responses represent either long-term physiological adaptations to facilitate homeostasis or reinforce direct genetic effects.

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

Children born small for gestational age are at increased risk of developing type 2 diabetes in adulthood. The satiety signal leptin that regulates food intake and energy expenditure might be a possible molecular link, as umbilical cord leptin levels are positively correlated with birth weight. In the present study, we examined whether common single nucleotide polymorphisms (SNPs) in the leptin (LEP; 19G>A) gene and its receptor (LEPR; Q223R and K109R) are associated with birth weight and adult metabolic risk factors for type 2 diabetes in twins. SNPs were genotyped in 396 monozygotic and 232 dizygotic twins (286 men and 342 women, mean age 25 years) recruited from the East Flanders Prospective Twin Survey. Data were analysed using linear mixed models. The LEPR K109R SNP was associated with birth weight (KK, KR and RR (95% confidence interval, CI): 2511 (2465-2557), 2575 (2516-2635) and 2726 (2606-2845) gram; P(additive)=0.001). Also the LEPR Q223R SNP showed a significant association with weight at birth (QQ, QR and RR (95% CI): 2492 (2431-2554), 2545 (2495-2595) and 2655 (2571-2740) gram; P(additive)=0.003). Furthermore, an interaction between the LEPR K109R and the Q223R SNP on birth weight was observed (P=0.014). G allele carriers of the LEP 19G>A SNP had higher high-density lipoprotein (HDL) cholesterol levels compared to 19A homozygotes (GX vs AA (95% CI): 1.62 (1.58-1.66) vs 1.49 (1.40-1.58) mmol l(-1); P(recessive)=0.013). This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood. Additionally, these results suggest that the LEP 19G>A SNP affect HDL cholesterol levels.