LEPR Polymorphisms Research Articles

Association analysis of polymorphisms in LEP (rs7799039 and rs2167270) and LEPR (rs1137101) gene towards the development of type 2 diabetes in North Indian Punjabi population.

Obesity is a major risk factor in aetiology of type 2 diabetes mellitus (T2DM). Leptin (LEP) is an anti-obesity hormone which regulates food intake, energy expenditure and glucose metabolism. The genetic variants in leptin and leptin receptor gene (LEPR) may play major role in the pathogenesis of T2DM and obesity. The current study aimed to investigate the association of polymorphisms in LEP (rs7799039, -2548G/A and rs2167270, 19G/A) and LEPR (rs1137101, 668A/G) gene with type 2 diabetes in North Indian Punjabi population. A total of 817 subjects were included for the present case-control study, consisting of 417 T2DM patients and 400 healthy controls. The anthropometric, physiometric and biochemical measurements were taken from all the subjects. The genotyping of LEP and LEPR gene variants were carried out by polymerase chain reaction based restriction fragment length polymorphism method (PCR-RFLP), followed by genotyping of 10% of the samples for each polymorphism by Sanger sequencing method for quality control measurement. The risk genotype frequencies were found to be significantly higher in T2DM cases than control subjects (rs7799039, p=0.001; rs2167270, p=0.019 and rs1137101, p=0.003). Under recessive genetic model LEPrs7799039 and LEPRrs1137101 polymorphism conferred 3.4 and 2.1 fold risk towards the development of T2DM after adjustment of various covariates (OR=3.44, 95%CI: 1.768-6.681, p=0.001 and OR: 2.12, 95%CI: 1.256-3.569, p=0.005, respectively). In the stratified analysis of LEP variant rs7799039 by age, gender, BMI and alcohol use, a significantly increased risk of T2DM was found in female, BMI≥23 and never drinking subgroups. However, in the LEPR variant rs1137101, significantly increased risk of T2DM was observed in age <50, male, BMI≥23 and never drinking subgroup. The A-G haplotype combination of rs7799039A and rs2167270G conferred significant 2 fold risk towards T2DM (OR=2.35, 95%CI: 1.34-4.12, p=0.002). In control group, the genetic variants rs7799039 and rs1137101 were significantly associated with levels of random blood sugar and low density lipoprotein cholesterol levels. The present study revealed the association of LEP rs7799039 and LEPR rs1137101 with type 2 diabetes mellitus, which suggest its predominant role in the estimation of type 2 diabetes mellitus in North Indian Punjabi population.

Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer.

The leptin is discharged from breast adipose tissue and is overexpressed in breast cancer (BC). Conflicting relation of leptin with BC was reported. We investigated this association and its impact on leptin level and disease characteristics. The study included 70 females (40 women with pathological proof of invasive BC patients and 30 controls). LEP and LEPR polymorphisms were evaluated by real-time PCR. Serum leptin was estimated by ELISA. Both LEPR and LEP disturbances increase the danger of BC where GG genotype and G allele frequencies of LEPR were higher in patients vs. control. GG genotype increases BC risk with OR (9.1) while G allele predisposes to disease with OR (3.8). Furthermore, LEP A allele was uniquely elevated in patients than healthy ones with OR (2.06). Precise relation of circulating leptin and its polymorphisms with predicting BC may authorize its utilization in early screening.

49P - Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer

BackgroundLeptin is produced by adipose tissue of breast and is overexpressed in Breast cancer. Association of leptin gene (LEP) and leptin receptor gene (LEPR) polymorphisms with Breast cancer are inconsistent. Only a very few studies have examined this biochemical and genetic variables so we planned to investigate this association and its impact on leptin level and disease characteristics. MethodsStudy included 70 females (40 women with pathological prove of invasive Breast cancer patients and 30 controls). Staging was done according to the American Joint Committee on Cancer 8th edition. LEP and LEPR polymorphisms were estimated by real time PCR. Serum leptin was measured by ELISA. ResultsBoth LEPR rs 1137101 and LEP rs 7799039 increase risk of breast cancer where GG genotype and G allele frequencies of LEPR rs 1137101 were significantly higher in patients than control [52.5% vs 16.7% and 68.8% vs 36.7%] (p = 0.002) and (p < 0.001) respectively. GG genotype increase risk of BC with [OR 9.1: 95% CI 2.30-35.94] while G allele predispose to disease with [OR 3.8: 95% CI 1.87 – 7.70]. Furthermore, LEP rs 7799039 A allele was markedly elevated in patients (61.2%) than healthy ones (43.3%) (p = 0.037) with [OR 2.06: 95% CI 1.05 – 4.08]. Leptin levels were markedly elevated than healthy ones (p < 0.001). ConclusionsResults clarified interesting relation of circulating leptin level and LEP and LEPR polymorphisms with predicting Breast cancer that may be implicated in pathogenesis of disease. Legal entity responsible for the studyMenoufia University. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

EFFECT OF LEPTIN RECEPTOR POLYMORPHISM ON EGYPTIAN CHILDREN WITH ENTAMOEBA HISTOLYTICA INFECTION

Entamoeba histolytica is a protozoan parasite that causes amebic colitis, an invasive disease responsible for as many as 100,000 deaths per year globally. Leptin signaling protects from amebiasis, with query molecular mechanism. This study aimed to evaluate the effect of leptin Receptor Q223R Polymorphism on Egyptian children with Entamoeba histolytica infection. After ethical clearance, blood and fecal samples were taken from one hundred children with E. histolytica and 100 children as control group. All children were subjected to anthropometric assessment. Entamoeba infected group was further assessed for severity of symptoms, cyst load, and ELISA for differentiation of E. histolytica from E. dispar. Q223R LEPR polymorphism then performed for both groups. RR was higher in children with E. histolytica group while QQ and QR were higher in control group. Heavy cyst count, severe underweight, severe symptoms, and median leptin level was higher in RR group compared to QQ & QR groups. The highest risk of R allele was severe underweight, severe symptoms and high leptin level.

LEPR polymorphisms and haplotypes in Mexican patients with colorectal cancer.

Obesity and colorectal cancer could be linked by adipocytokines, which are proteins associated with cell proliferation. High levels of the adipocytokine leptin promote the development of colorectal cancer through its receptor. To determine the association between c.326A>G and c.668A>G LEPR gene polymorphisms and colorectal cancer. DNA was extracted from the peripheral blood of 147 patients with sporadic colorectal cancer and 134 healthy people. Genotypes were obtained by PCRRFLP and the association was determined by the odds ratio (OR) test using the SPSS™, version 10.0, program. Haplotype frequencies and linkage disequilibrium were estimated by the Arlequin, version 3.5, software. Both polymorphisms were in Hardy-Weinberg equilibrium. Only the c.326A>G heterozygous genotype revealed an increased risk for colorectal cancer development (OR=1.81, 95% CI=1.04-3.16, p=0.04). The AG haplotype showed a significant association with colorectal cancer (OR=0.58, 95% CI=0.35-0.96, p<0.03). Linkage disequilibrium between the variants was only evident for the patients group (r2=0.36). Our results suggest that AG individuals heterozygous for the c.326A>G LEPR variant have a higher risk of colorectal cancer development whereas the AG haplotype (c.326A/c.668G) has a protective effect in the Mexican population.

Genetic aspects of metabolic disorders in pregnant women with pathological weight gain

Polymorphism of the leptin receptor gene (LEPR) has been shown to be linked to obesity-related metabolic markers and phenotype. Therefore, we hypothesized that the Gln233Arg LEPR polymorphism is related to metabolic changes in pregnancy and the risk of excessive gestational weight gain (GWG). A total of 97 pregnant women with a singleton gestation were enrolled from April 2016 until December 2018. Genetic variants of LEPR were analyzed by real-time polymerase chain reaction, leptin by enzyme-linked immunosorbent assay, lipid profile, and carbohydrate status were assessed in the first, and third trimesters of pregnancy. The recommended GWG was diagnosed in 34.0%, insufficient in 19.6%, and excessive in 46.4% patients. Statistical analysis revealed that 20.6% patients were with AA genotype, 50.5% – AG genotype, and 28.9% – GG genotype. The frequency of GG-alleles carriers of the LEPR Gln233Arg gene in the group of excessive GWG patients was 3 times higher compared to recommended GWG patients. Thus, the inheritance of pathological G-homozygotes increases the risk of excessive weight gain by 7 times, compared to carriers of the AA genotype. LEPR GG polymorphism was significantly associated with high levels of triglycerides, total cholesterol, lipoprotein low and very low density, and leptin compared to homozygous А-carriers in the third trimester of pregnancy. In pregnant women with GG polymorphism, the glucose level, insulin level, and HOMO-IR index were significantly increased compared to women with AA genotype in late pregnancy. In the group with excessive GWG, the presence of GG-alleles of the LEPR gene was accompanied by a higher level of hyperleptinemia, compared to carriers of AA-genotype. Inheritance of pathological G-homozygotes was associated with hyperlipidemia, leptin resistance with high leptin serum levels, and increased insulin resistance, which was especially manifested in excessive GWG. In our opinion, excessive GWG can be seen as a marker of the mother's genotype and genetic predisposition to the development of metabolic diseases after delivery.

Genetic susceptibility of Iraqis for obesity and type 2 diabetes: LEPR gene polymorphisms

Prevalence of obesity and diabetes over world encouraged researchers to expand their studies about genetic predisposition factors which increase individuals' risk for diseases. LEPR gene encodes for leptin receptor which regulates body weight, energy expenditure and insulin sensitivity by binding with adipose derived hormone (leptin). Therefore we sequenced LEPR's promoter, coding exons, exon-intron boundaries and 3′UTRin 45 Iraqi individuals (24 were diagnosed with type 2 diabetes and 21 were not). Seventeen polymorphisms have been detected in this study, 6 in promoter region, 5 in coding exons, 5 in introns (2 were novel) and I Ins/Del in 3′UTR. Type 2 diabetic carriers of rs1137101 in exon 6 were 75% in comparison to non-diabetics (52.4%). Also 50% and 33.3% from diabetic patients and non-diabetics, respectively were carrying p.S343S in exon 9. GC allele in exon 14 increased the BMI of diabetics to 34.6 ± 7.8 but it was 32.4 ± 4.4 in patients with GG allele and both of them were higher in type 2 diabetics than other group (30.2 ± 5.2 and 29.9 ± 2.5, respectively). BMI of diabetic patients with AA allele (P1019P) in exon 20 was 35.7 ± 4 but it was 32.7 ± 5.9 in patients with GG allele, the same was in non-diabetics which was 33.3 ± 4 and 30 ± 3.7, respectively. Also CTTTA insertion allele increased the BMI of diabetics to 35.7 ± 4 in comparison to CTTTA deletion allele as well as 33.3 ± 4 and 29.6 ± 3.5 in other group, respectively. We have concluded that LEPR polymorphisms may increase the risk of developing type 2 diabetes in individuals with BMI ≥ 30 and in general LEPR is a candidate gene for susceptibility to obesity and its outcomes.

Influence of K656N Polymorphism of the Leptin Receptor Gene on Obesity-Related Traits in Nondiabetic Afro-Caribbean Individuals.

Background: Ethnic variations have been reported in allelic frequencies of the leptin receptor gene (LEPR) with population-specific effects. We aimed to explore the association of LEPR polymorphisms with obesity, metabolic syndrome (MetS), and leptin levels in Afro-Caribbean nondiabetic subjects. Methods: Genotypic analysis of three LEPR polymorphisms (K109R, Q223R, and K656N) was performed using TaqMan allelic discrimination assays. Associations were measured with phenotypic variables, including body mass index (BMI), waist circumference (WC), and leptin levels. Linear and logistic regressions were performed to evaluate the effects of single-nucleotide polymorphisms (SNPs). Results: Mean age was 46 ± 12 years. Among the 375 participants, 29.3% were obese, 36.3% had abdominal obesity, and 18.1% had MetS. Significant association between BMI (P < 0.002) and WC (P < 0.005) was observed for K656N, whereas the associations were not statistically significant for the other two SNPs. No association was found with leptin levels for the three SNPs. The variant allele frequencies for LEPR 109R, 223R, and 656N were 0.16, 0.46, and 0.20, respectively. In dominant models, the variant allele 656N (GC/CC vs. GG) was associated with prevalence of obesity [odds ratio (OR) 1.82; P = 0.012] and abdominal obesity (OR 2.00; P = 0.007), but not significantly with prevalence of MetS (OR 1.72; P = 0.029). Individuals carrying four variant alleles of the three SNPs had a significantly higher risk of obesity (OR 2.86; P = 0.032) than those carrying none variant allele. Conclusion: Our results suggest an influence of K656N polymorphism in the LEPR gene on obesity and abdominal obesity in this Afro-Caribbean population.

Variability in the leptin receptor gene and other risk factors for post-transplant diabetes mellitus in renal transplant recipients

Aim Post-transplant diabetes mellitus (PTDM) is one of the main complications after kidney transplantation. It is known that leptin plays an important role in glucose metabolism and mutations in the leptin receptor gene (LEPR) are responsible for different complications in renal transplant recipients. We aimed to analyse the association of polymorphisms in LEPR with the development of PTDM in these patients. Methods A total of 315 renal transplant recipients were genotyped for the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms. The impact of these genetic variables together with other clinical and demographic parameters on PTDM risk was evaluated in a multivariate regression analysis. Results The 223Arg variant showed a significant association with PTDM risk [OR = 3.26 (1.35–7.85), p = 0.009] after correcting for multiple testing. Carriers of this variant also showed higher BMI values (26.95 ± 4.23) than non-carriers (25.67 ± 4.43, p = 0.025). In addition, it was BMI at transplant and not the BMI increment in the first year after grafting that was associated with PTDM (p > 0.00001). Haplotype analyses did not reveal significant associations. Conclusions Our result show, for the first time to our knowledge, that genetic variability in the LEPR may contribute significantly to the risk for PTDM in renal transplant recipients. KEY MESSAGES The LEPR Gln223Arg polymorphism significantly contributes to the development of PTDM in renal transplant recipients. The effect of the 223Arg variant on PTDM is strongly modulated by the age of the recipient. The 223Arg variant in the leptin receptor is related to higher BMI in renal transplant recipients.

Leptin and Leptin receptor polymorphisms, plasma Leptin levels and obesity in Tunisian volunteers.

Adipose tissue is an important endocrine organ that secretes a number of adipokines, like Leptin (LEP). The aim this study was to investigate the prevalence of single nucleotide polymorphisms in LEP gene (LEP 3'UTR A/C, -2548G/A) and LEPR (K109R and Q223R) and their association with Leptin level and obesity. We recruited 169 non-obese (body mass index [BMI]=24.51-3.69kg/m2 ) and 160 obese (BMI=36-4.78kg/m2 ) patients. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism, BMI was calculated, and Leptin level was measured by ELISA. Statistical analyses were performed by spss19.0. According to LEP 3'UTR A/C polymorphism, AC and CC genotype carriers had higher Leptin levels than AA genotype carriers, respectively, 31[0.05-148.8] (P=.008) vs 41[0.05-111.6] (P=.003). The K109R polymorphism was associated with obesity (P=.025) and seems to significantly decrease the LEP levels (P<.001). Concerning LEP G2548A polymorphism, our results showed that the OR of obesity associated with 2548 AA/GG was 1.87[1.106-2.78] P=.028 vs 1.41[1.035-1.85] P=.045 for 223AA/GG polymorphism. In our haplotype analysis, one haplotype seems to be the more protective and one other seems to be the highest risk to obesity. LEP 3'UTR A/C and LEPR K109R polymorphisms were associated with Leptin level and obesity.

Obesity phenotype in relation to gene polymorphism among samples of Egyptian children and their mothers

Obesity is complex heterogeneous disease controlled by genes, environmental factors, and their interaction. Genetic factors account for 40–90% of the body mass index variations. Body mass index (BMI) of children correlates more closely with maternal than paternal BMI. So, this studu was aimed to investigate the role of leptin receptor LEPR Gln223Arg, the uncoupling protein 2 (UCP2 G 866 A) and insulin receptor gene (INSR exon 17) polymorphisms in the pathogenesis of obesity. A cross-sectional study executed on 130 children and their obese mothers; classified into 2 groups according to their BMI. The 2 groups were evaluated regarding the anthropometry. Restriction fragment length analysis for LEPR Gln223Arg, UCP2 -866 G/A and INSR exon 17 polymorphisms were applied. It was reported that increased risk of obesity was found in LEPR AG + AA genotype and the A allele. Significant statistical difference was detected only in female children. Concerning UCP2, the AG followed by the GG genotype was the most frequent in all groups and the G allele was the mostly present in obese mothers and obese male children but with no statistical significance. There was difference in the INSR genotype and alleles between groups, but this difference was not statistically significant. This study concluded that the LEPR Gln223Arg, UCP2 G 866 A and INSR exon 17 polymorphisms are related to obesity in Egyptian population. Further researches on larger population are recommended to ascertain the implications of LEPR, UCP2 and INSR polymorphisms in obesity.

LEPR polymorphism may affect energy balance during weight loss among Brazilians obese adolescents

ObjectiveLeptin is an adipokine released mainly by adipose tissue, with many functions including regulation of energy balance. However, little is known about the effect of LEPR polymorphism on orexigenic and anorexigenic neuropeptides. Thus, the aim of the present study is to verify the influence of LEPR polymorphism (rs2767485) on serum orexigenic (NPY, MCH and AgRP) and anorexigenic (Leptin and α-MSH) neuropeptides levels among obese adolescents submitted to 1year of multicomponent weight loss therapy. MethodsSeventy-six adolescents with obesity were enrolled in 1year of weight loss therapy including clinical, nutritional, psychological and exercise-related. Blood samples were collected to analyze neuropeptides (NPY, MCH, AgRP and leptin) and LEPR genotyping. Visceral fat was measured by ultrasound and body composition was measured by plethysmography. The parameters were measured at baseline and after one year. Adolescents were grouped according to genotype (TT or CT+CC group). Effect of the weight loss therapy was analyzed through ANOVA and Wilcox, according to normality. Statistic value was set at <0.05. ResultsC-allele carriers have the orexigenic neuropeptides (NPY, AgRP and MCH) levels statistically higher when compared with TT group, at baseline. Furthermore, TT group seems to respond better to the therapy by a greater delta on BMI. Indeed, the data suggest a concomitant increased of AgRP levels in CT+CC genotypes, after weight loss therapy. ConclusionBoth groups responded to the weight loss intervention, however wildtypes (TT) appear to respond to the intervention most optimally with C carries, where post intervention reduction in BMI was significantly greater in wildtypes. The leptin receptor polymorphism seems to affect neuroendocrine regulation of energy balance among adolescents with obesity.

LEPR Gene Polymorphism and Plasma Soluble Leptin Receptor Levels are Associated with Polycystic Ovary Syndrome in Han Chinese Women

To investigate the association of LEPR polymorphisms and plasma leptin and soluble leptin receptor (sOB-R) levels with polycystic ovary syndrome (PCOS) in Chinese women. LEPR Lys109Arg (rs1137100) and Gln223Arg (rs1137101) polymorphisms of PCOS patients and the controls were genotyped. Plasma leptin and sOB-R levels of two groups were measured. The genotypic distributions of Lys109Arg (rs1137100) differed between the PCOS and control groups. Plasma sOB-R levels increased significantly in PCOS patients and were associated with PCOS independent of BMI. Furthermore, luteinizing hormone, triglyceride and fasting blood glucose correlated significantly to PCOS patients' sOB-R levels. LEPR Lys109Arg (rs1137100) was associated with PCOS susceptibility and genotype AA was deduced to be a protective factor for PCOS; sOB-R levels might be recognized as a new indicator for the severity of PCOS.

Circulating leptin, soluble leptin receptor, free leptin index, visfatin and selected leptin and leptin receptor gene polymorphisms in sporadic breast cancer.

Leptin and visfatin are implicated in breast cancer risk but studies accounting for bioavailability of leptin are sparse. Reports on the association of leptin gene (LEP) and leptin receptor gene (LEPR) polymorphisms with breast cancer are also inconsistent. Only a very few studies have examined biochemical and genetic variables concomitantly in the same cohort. A matched pairs study was carried out to ascertain whether plasma leptin, soluble leptin receptor, free leptin index (leptin/soluble leptin receptor), serum visfatin and selected LEP and LEPR polymorphisms are risk factors for sporadic breast cancer. Newly diagnosed sporadic breast cancer patients (N=80) were matched for age, body mass index (BMI) and menopausal status with healthy controls. Plasma leptin, soluble leptin receptor and serum visfatin were measured by enzyme-immunoassay. LEP -2548 A/G and LEPR K109R, LEPR Q223R polymorphisms were determined by genotyping. Leptin (p=0.0234), leptin/BMI (p=0.0468), free leptin index (p<0.0001) and visfatin (p=0.0002) were significantly higher and soluble leptin receptor (p<0.0001) was significantly lower in patients. LEPR gene K109R A/G polymorphism increased breast cancer risk (odds ratio: 4.125). Multivariate analysis confirmed that leptin, soluble leptin receptor, free leptin index and G109 (R109) allele of the LEPR gene K109R polymorphism are risk factors for breast cancer. When stratified by menopausal status free leptin index and soluble leptin receptor remained as risk factors irrespective of menopausal status while LEPR gene K109R A/G polymorphism remained as a risk factor only in the postmenopausal group.

The associations of LEPR and H-FABP gene polymorphisms with carcass traits in pigs

The aim of this study was to assess the impact of polymorphisms in porcine LEPR and H-FABP genes on carcass and meat quality traits in population of Large White x Landrace crossbreeds. The genomic DNA samples obtained from in total of 180 animals (86 boars and 94 sows) were genotyped using PCR-RFLP methods. The association analyses were carried out in relation to evaluate back-fat thickness, proportion of valuable meat parts, MLT area and proportion of thigh using One-way ANOVA procedure. The allele frequencies were as follows: H-FABP/HinfI H 0.31 and h 0.69, H-FABP/HaeII 0.65 and 0.35, and LEPR/HpaII 0.61 and 0.39. The average values of heterozygosity (0.37) and FIS index (0.17) indicated in population the prevalence of homozygous genotype across all evaluated loci. The statistical analyses showed significant effects on selected production traits only for H-FABP/HinfI (p &lt; 0.001) and LEPR/HpaII (p &lt; 0.0001) loci. The obtained results indicated the positive effect of H-FABP/HinfIH and LEPR/HpaIIA alleles in order to improvement of the economically important parameters for breeders.

Complementary Effects of Genetic Variations in LEPR on Body Composition and Soluble Leptin Receptor Concentration after 3-Month Lifestyle Intervention in Prepubertal Obese Children.

In obese individuals, weight loss might be affected by variants of the adipokine-encoding genes. We verified whether selected functional single nucleotide polymorphisms in LEP, LEPR and ADIPOQ are associated with changes in serum levels of the respective adipokines and weight loss in 100 prepubertal obese (SDS-BMI > 2) Caucasian children undergoing lifestyle intervention. Frequencies of the -2548G > A LEP, Q223R LEPR, K656N LEPR, -11377C > G and -11426A > G ADIPOQ polymorphisms were analyzed by restriction fragment length polymorphism. Serum adipokine and soluble leptin receptor (sOB-R) concentrations were measured using the ELISA method. Among the analyzed polymorphisms, only LEPR polymorphisms were associated with changes of SDS-BMI or sOB-R concentrations in children after therapy. Carriers of the wild-type K665N and at least one minor Q223R allele had the greatest likelihood of losing weight (OR = 5.09, p = 0.006), an increase in sOB-R (ptrend = 0.022) and decrease in SDS-BMI correlated with the decrease of fat mass (p < 0.001). In contrast, carrying of the wild-type Q223R and at least one minor K665N allele were associated with a decrease in sOB-R concentrations and a decrease in SDS-BMI correlated with a decrease in fat-free mass (p = 0.002). We suggest that the combination of different LEPR variants, not a single variant, might determine predisposition to weight loss in the prepubertal period.

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.

Genetic polymorphisms associated with overweight and obesity in uncontrolled Type 2 diabetes mellitus.

Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM.

Effect of ghrelin and leptin receptors genes polymorphisms on production results and physicochemical characteristics of M. pectoralis superficialis in broiler chickens

Ghrelin and leptin and their receptors GHSR and LEPR regulate food intake, the processes in adipose tissue, and the body’s energy homeostasis in mammals. The aim of the present study was to determine the effect of GHSR/Csp6I and LEPR/Bsh1236I polymorphisms on the meat production parameters of broiler chickens reared to 42 days of age. In 318 fast-growing Hubbard Flex and Ross 308 chickens, g.3051C &gt; T substitution at the GHSR locus and a GGTCAA deletion at positions g.3407_3409del and g.3411_3413del were identified. The use of restriction enzyme Bsh1236I showed the presence of two transitions g.352C &gt; T and g.427G &gt; A in LEPR locus. The chickens were classified into four GHSR/Csp6I and into five LEPR/Bsh1236I diplotypes. GHSR and LEPR polymorphisms were found to influence final bodyweight, daily gain, dressing percentage without giblets, proportion of giblets and the quality characteristics of M. pectoralis superficialis. GHSR/Csp6I and LEPR/Bsh1236I had an effect on pH24 h (P &lt; 0.05) and lightness (L*) of M. pectoralis superficialis (P &lt; 0.05), whereas GHSR/Csp6I influenced shear force (P &lt; 0.05) and thawing loss (P &lt; 0.05). GHSR/Csp6I and LEPR/Bsh1236I were found to have no effect on the abdominal fat content in chicken carcasses. Single nucleotide polymorphisms reported in the present study could be used in breeding programs as selection markers for growth traits and poultry meat quality.