Leptin Single Nucleotide Polymorphisms Research Articles

Association of Leptin Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population

Background Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05). No significant difference in plasma leptin levels was detected between RA patients and controls (P > 0.05). Conclusion Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.

Investigation of Leptin and its receptor (LEPR) for single nucleotide polymorphisms in colorectal cancer: A case-control study involving 2,306 subjects.

e16100 Background: Colorectal cancer is a leading cause of cancer deaths, with poor prognosis. Some studies have reported that obesity and overweight are risk factor for the development of CRC. Leptin ( LEP) and its receptor ( LEPR) single nucleotide polymorphisms (SNPs) might regulate energy balance and be implicated in the development of CRC. The aim of this case-control study was to assess the association of LEP rs2167270 G > A, rs7799039 A > G, LEPR rs6588147 G > A, rs1137100 G > A and rs1137101 G > A SNPs with susceptibility to CRC in Eastern Chinese Han population. Methods: 1,003 CRC cases and 1,303 matched controls was compared. Five functional SNPs in LEP and LEPR genes were chosen to evaluate the correlation of these chosen SNPs with CRC susceptibility. We used the SNPscan genotyping assay to genotype LEP and LEPR SNPs. Results: A significantly decreased risk of CRC was found to be associated with the LEPR rs6588147 polymorphism (GA vs. GG: crude P= 0.007 and GA/AA vs. GG: crude P= 0.018). With adjustments for risk factors (e.g. age, gender, drinking, BMI and smoking), these associations were not changed. In subgroup analyses, the association of LEP rs2167270 with a decreased risk of CRC was found in the ≥61 years old subgroup. For LEPR rs1137100, the association of this SNP with an increased susceptibility of CRC was found in the BMI < 24 kg/m2 subgroup. In subgroup analyses for LEPR rs6588147, we identified that this locus also decreased the susceptibility of CRC in the male subgroup, < 61 years old subgroup, never smoking subgroup and never drinking subgroup. For LEPR rs1137101, the relationship of this polymorphism with a decreased susceptibility to CRC was found in the never drinking subgroup. Conclusions: The present study highlights that LEPR rs6588147, rs1137101 and LEP rs2167270 may decrease the risk of CRC. However, LEPR rs1137100 is associated with susceptibility to CRC. Further case-control studies with larger sample sizes should be conducted to validate our findings.

Associations of maternal diet and placenta leptin methylation

BackgroundMaternal diet is an important factor in prenatal development that also has implications for disease risk later in life. The adipokine leptin is a key regulator of energy homeostasis and may be involved in the association between maternal nutrition, maternal obesity, and infant outcomes. DNA methylation of placenta genes may occur in response to exposures and may program subsequent infant development. This study examined maternal diet, placenta leptin gene DNA methylation, and neonatal growth in a sample of healthy neonates and their mothers. MethodsMothers and their healthy neonates (N = 135) were recruited within 1–2 days following delivery at Women and Infants Hospital in Providence, RI. A structured interview was conducted to assess maternal dietary intake. Maternal pre-pregnancy weight, weight gain during pregnancy, maternal health, medications, and vitamin use were obtained from medical records. Bisulfite pyrosequencing was used to measure methylation of CpG sites in the promoter region of the placenta leptin gene and determine genotype of the leptin single nucleotide polymorphism (SNP) rs2167270, which is known to influence leptin methylation. Bivariate analyses and linear regression models were used to evaluate associations of demographics, diet, and mean leptin methylation. ResultsGenotype was a significant predictor of placenta leptin DNA methylation (p < .01), and after controlling for this and other relevant maternal and infant covariates, lower levels of leptin methylation were significantly associated with greater intake of carbohydrates (p < .05), in particular added sugars (p < .05) and white/refined carbohydrates (p < .05). Total caloric intake was also associated with placenta leptin methylation (p < .05), however after controlling for relevant covariates, significance diminished to trend-level. There were no significant associations of placenta leptin methylation and intake of protein (p > .05) or fat (p > .05). ConclusionThese findings underline the importance of intake of carbohydrate consumption for methylation of the placenta leptin gene. Because methylation reduces gene transcription, lower methylation may indicate a placenta response to high caloric intake and carbohydrate food that would result in higher levels of this hormone during fetal development. Further investigation of the developmental ramifications of epigenetic changes to placenta leptin methylation should be pursued.

Second Trimester Maternal Leptin Levels Are Associated with Body Mass Index and Gestational Weight Gain but not Birth Weight of the Infant

Introduction: Obesity is increasing among the pregnant population. Leptin has an important role in the regulation of energy balance and hunger. The aim of this study was to investigate the association between maternal leptin levels with maternal obesity, gestational weight gain (GWG), single nucleotide polymorphisms (SNPs) within the leptin gene, and the age-adjusted birth weight of the child. Material and Methods: Maternal leptin levels (n = 740) and SNPs (n = 504) were analyzed in blood samples taken within the Uppsala Biobank of Pregnant women at pregnancy weeks 16–19. Results: Maternal leptin levels differed significantly between body mass index (BMI) groups. Normal weight women had the lowest median leptin levels and levels increased with each BMI group. Leptin SNP genotype was not associated with leptin levels or BMI. There was also no association between maternal leptin levels and age-adjusted birth weight of the child except for a negative association between leptin levels and birth weight in the morbid obese group. Discussion/Conclusion: Maternal BMI was identified as the best positive explanatory factor for maternal leptin levels. Leptin was a strong positive explanatory factor for GWG. Birth weight of children of uncomplicated pregnancies was, however, dependent on maternal height, BMI, GWG, and parity but not leptin levels, except for in morbid obese women where a negative association between maternal leptin levels and birth weight was found. We speculate that this indicates altered placental function, not manifested in pregnancy complication. We conclude that maternal leptin levels do not affect the birth weight of the child more than BMI, GWG, and parity.

Leptin gene polymorphism (rs7799039; G2548A) is associated with changes in serum lipid concentrations during pregnancy: a prospective cohort study.

Little is known about the effects of leptin and leptin receptor polymorphisms on lipid changes during pregnancy. The aims of this study were to evaluate the associations between the single nucleotide polymorphisms (SNPs) of leptin and leptin receptor genes and the lipid concentrations during pregnancy; and to test whether dietary intake is a mediator in these associations. A prospective cohort of 154 pregnant women was followed up in Rio de Janeiro, Brazil during the following gestational periods: 5-13th, 20-26th and 30-36th weeks. HDL-C, total cholesterol (TC) and triglyceride (TG) were measured by the enzymatic colorimetric method, and LDL-C was calculated. DNA was extracted by the phenol-chloroform method, and leptin (G2548A, rs7799039) and leptin receptor SNPs (Q223R; rs1137101 and K109R; rs1137100) were genotyped using real-time PCR. Statistical analyses included linear mixed-effect models. Women with the AA genotype of G2548A polymorphism reported a higher fat and total energy intake and had a higher increase in TG concentration during pregnancy than women with AG or GG genotype. The association between G2548A SNP and TG concentrations was not attenuated by adjusting for total lipid (g) and energy (kcal) intake. We did not observe significant associations between the Q223R and K109R SNPs and the lipid concentrations. Women homozygous for the A allele of the leptin SNP (G2548A) had a higher increase in TG concentrations per gestational week compared with women with the AG or GG genotype. This is an exploratory and hypothesis-generating study, and the results need confirmation in studies with larger sample sizes.'

Leptin -2548 G/A polymorphisms are associated to clinical progression of oral cancer and sensitive to oral tumorization in nonsmoking population.

Oral cancer is causally associated with environmental carcinogens, and the susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype-dependent. Leptin (LEP) and leptin receptor (LEPR) both play a crucial role in the mediation of physiological reactions and carcinogenesis and may serve as a candidate biomarker of oral cancer. The current case-control study aimed to examine the effects of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) single-nucleotide polymorphisms (SNPs) with or without interacting to environmental carcinogens on the risk for oral squamous cell carcinoma. The SNPs of three genetic allele, from 567 patients with oral cancer and 560 healthy controls in Taiwan were analyzed. The results shown that the patients with polymorphic allele of LEP -2548 have a significant low risk for the development of clinical stage (A/G: adjusted odds ratio [AOR] = 0.670, 95% confidence interval [CI] = 0.454-0.988, P < 0.05; A/G + G/G: AOR = 0.676, 95% CI = 0.467-0.978, P < 0.05) compared to patients with ancestral homozygous A/A genotype. In addition, an interesting result was found that the impact of LEP -2548 G/A SNP on oral carcinogenesis in subjects without tobacco consumption is higher than subjects with tobacco consumption. These results suggest that the genetic polymorphism of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) were not associated to the susceptibility of oral cancer; SNP in LEP -2548 G/A showed a poor clinicopathological development of oral cancer; population without tobacco consumption and with polymorphic LEP -2548 G/A gene may significantly increase the risk to have oral cancer.

Association of single nucleotide polymorphisms in leptin (LEP) and leptin receptor (LEPR) genes with backfat thickness and daily weight gain in Ukrainian Large White pigs

Leptin (LEP) and leptin receptor (LEPR) genes play an important role in the regulation of fat deposition and other commercially important traits in pigs and this regulation is known to be breed-specific. The aim of the present study was to investigate the presence and frequency of LEP polymorphisms g.2845A > T, g.3996T > C, and LEPR polymorphisms c.232A > T, c.915C > T and c.2856C > T in Ukrainian Large White pigs, and to determine whether these polymorphisms are associated with the following traits: backfat thickness at the 10th rib, backfat thickness at the 6-7th rib, backfat thickness at sacrum and average daily weight gain. The study was conducted on 108 Ukrainian Large White purebred female pigs. Genotyping of LEP and LEPR polymorphisms was performed using RCR-RELF technique. The study demonstrated that the LEP SNP g.2845A > T was segregating in the population of Ukrainian Large Whiter pigs studied with almost equal frequencies of the alternative alleles being observed. The LEP SNP g.3996 T > C was absent in Ukrainian Large White pigs with all the animals having g.3996CC genotype. The LEPR SNP c.915C > T was segregating in the pig population studied with c.915C allele frequency dominating. Segregation was also observed for the LEPR SNP c.2856 C > T with an almost equal frequency of the alternative alleles. The LEPR SNP c.232A > T was polymorphic with the frequency of the alternative alleles c.232A and c.232T being 0.25 and 0.75 respectively. No association was established between any of the traits investigated and the LEP SNP g.2845 A > T, LEPR SNP c232A > T, and LEPR SNP c.915C > T. The LEPR SNP c.2856C > T was associated with backfat thickness at the level of 6-7th and 10th ribs with c.2856TT genotype having lower backfat thickness compared to c.2856CC and c.2856CT. The LEPR SNP c.2856C > T was also associated with average daily weight gain which was lower in animals with c.2856TT genotype. Results of the study suggest that LEPR SNP c.2856C > T can be considered as a genetic marker for subcutaneous fat deposition and average daily weight gain in Ukrainian Large White pigs. This marker can be of particular importance in breeding programmes aiming to modify the carcass structure and pigs growth rate.

Association of leptin, toll-like receptor 4, and chemokine receptor of interleukin 8 C-X-C motif single nucleotide polymorphisms with fertility traits in Czech Fleckvieh cattle

ObjectiveThe use of genetic markers can help to enhance reproduction in cattle, which is a very important trait for profitability in dairy production systems. This study evaluated the association between genotypes of leptin (LEP), toll-like receptor 4 (TLR4), and chemokine receptor of interleukin 8 C-X-C motif (CXCR1) genes and fertility traits in Czech Fleckvieh cattle.MethodsPhenotypic data from 786 Czech Fleckvieh cows raised on 5 farms in the Czech Republic were used, along with information from the 1st three parities. To determine genotype, the polymerase chain reaction– restriction fragment length polymorphism method was used.ResultsExcept for LEP g.-963C>T, all studied genotype frequencies of single nucleotide polymorphisms (SNPs) were distributed according to the Hardy-Weinberg equilibrium. Two LEP SNPs (g.-963C>T and c.357C>T) were associated with the age at the 1st calving, days open (DO), pregnancy rate after 1st service (PR), and calving interval (CLI). In LEP g.-963C>T the TT genotype heifers firstly calved 24 days earlier than CC genotype and the CT genotype cow showed a tendency for shorter DO and higher PR. In LEP c.357C>T we observed longer CLI and DO period in TT cows. In general, we can propose the TT genotype of g.-963C>T as favorable and the TT genotype of c.357C>T as unfavorable for a cow’s fertility. Heterozygotes in TLR4 c.-226C>G were significantly associated with shorter CLI, and presented a nonsignificant tendency to be associated with higher PR. In CXCR1 c.777 C>G, we did not observe any relationship of this SNP with reproduction.ConclusionOverall, the results showed that LEP could be an effective marker for improving reproduction in Czech Fleckvieh cattle. This study also provides novel insights into the relationship between TLR4 and CXCR1 SNPs and reproduction in dual-purpose cattle.

Effects of leptin and leptin receptor SNPs on clinical- and metabolic-related traits in apparent treatment-resistant hypertension

Leptin is associated to the lack of blood pressure control as well as target organ damage in resistant hypertensive (RH) subjects. Single-nucleotide polymorphisms (SNPs) rs7799039 and rs1137101 in leptin (LEP) and leptin receptor (LEPR) genes, respectively, are associated with cardiovascular disease and metabolic syndrome. We evaluated the association of these two SNPs with clinical and biochemical features in 109 apparent treatment-RH subjects (aTRH) and 125 controlled hypertensives. Homozygous genotypes GG (n = 43) vs. AA (n = 14) for rs7799039 and AA (n = 34) vs. GG (n = 26) genotypes for rs1137101 were compared in aTRH subjects. There was no difference in leptin levels among both SNPs. On the other hand, LEP SNP (GG vs. AA) associated with the levels of glycated haemoglobin (6.4 ± 1.4 vs. 7.8 ± 2.3%, p = 0.03), insulin (8.6 ± 4.6 vs. 30.6 ± 27.7 uUI/mL, p = 0.01), HDL-cholesterol (51 ± 16 vs. 39 ± 11 mg/dL, p = 0.001) and PWV (9.5 ± 2.1 vs. 11.2 ± 2.8 m/s, p = 0.03). LEPR SNP (AA vs. GG), associated with heart rate (69 ± 12 vs. 67 ± 12 bpm, p = 0.03), fat mass (31 ± 11 vs. 24 ± 8 kg, p = 0.03) and triglycerides levels (175 ± 69 vs. 135 ± 75 mg/dL, p = 0.03). These findings may be clinically useful for identifying a group of aTRH who may have a LEP and/or LEPR gene variants, which may predispose this specific group to worse or better outcomes.

Modification of the association between the polymorphisms of adipokine genes and serum adipokine levels by vitamin D status in African Americans: The Jackson Heart Study

BackgroundAdipokines, such as leptin and adiponectin play a central role in whole‐body homeostasis and are associated with metabolic risk factors like insulin resistance, lipid disorders and obesity. African Americans (AA) have high prevalence of vitamin D deficiency (VDD) and evidence suggests that VDD may increase metabolic risk by modifying adipokine production.ObjectiveUsing the data of 3003 participants (61.9% female, mean age 54.58 years) from the Jackson Heart Study cohort we examined whether associations between single nucleotide polymorphisms (SNP) in the human leptin (LEP) and the human leptin receptor (LEPR) genes with leptin level and SNPs in ADIPOQ gene with adiponectin level were modified by vitamin D status in adult AA.MethodsSerum 25‐hydroxy‐vitamin D&lt; 20ng/ml was used to define VDD. In total, we selected 19, 88, and 18 tagging SNPs in LEP, LEPR and ADIPOQ gene respectively. IMPUTE2 software and reference phased data from the 1000G project were used for genotype imputation. Under the assumption that each gene represents a separate hypothesis, linear regression models were run to see the associations between SNPs with leptin and adiponectin levels adjusting for age, gender, education status, physical activity, obesity, smoking, alcohol intake, European ancestry and multiple testing separately for VDD and non‐VDD participants. Log transformed values of leptin and adiponectin were used for all analysis. A secondary analysis was done with the mean annualized 25‐hydroxy‐vitamin D derived using a cosinor model.ResultsAmong the LEP SNPs, the C allele of the rs11763517 [beta‐coefficient, β= 0.03; P=4.6×10−4] was associated with increased serum leptin levels, while the T allele of the rs17151922 [β= −0.029; P=9.0×10−5] and the A allele of the rs17151919 [β= −0.10; P=1.8 x10−16] were associated with decreased serum leptin levels in VDD participants. The rs17151919 [β= −0.098; P=7.0 x10−5] was also related with decreased leptin levels in non‐VDD participants. In addition, the A allele of the LEP SNP rs17151913 [β= 0.069; P=2.3 x10−3] was associated with increased leptin levels in them. None of the AdipoQ SNPs showed any association with adiponectin level among non‐VDD participants. However for VDD participants, carriers of the C allele of the rs4632532 [β= −0.034; P=2.3 x10−4], the T allele of the rs9842733 [β= −0.043; P=2.5 x10−3] and the G allele of the rs9877202 [β= −0.06; P=3.2 x10−5] presented decreased serum adiponectin levels. The pattern of the association remained similar in the secondary analysis.ConclusionOur findings demonstrate that the associations between adipokine SNPs and adipokine levels could be modified by vitamin D status in AA. Therefore, vitamin d status should be taken into consideration when evaluating the genetic variation of specific alleles for adipokines.Support or Funding InformationThis research was supported by the Intramural Research Program of the National Institutes of Health. The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities.

Association study between single nucleotide polymorphisms in leptin and growth traits in Cyprinus carpio var. Jian.

Leptin is a hormone that affects the regulation of body weight, energy expenditure, fat metabolism, food intake, and appetite. In this study, we cloned the jlLEP-A1 and jlLEP-A2 genes in Jian carp (Cyprinus carpio var. Jian) and performed an association analysis between identified polymorphisms and growth traits. Three polymorphisms in exons of jlLEP-A1 (A1-T113C) and jlLEP-A2 (A2-G415A and A2-G427A) were identified, and genotyped by the polymerase chain reaction - restriction fragment length polymorphism method in 263 female and 294 male Jian carp. All three SNPs were missense mutations. Association analysis revealed that the three SNPs were significantly associated with growth traits in male Jian carp. Only SNP A1-T113C was significantly associated with growth traits in female Jian carp. Analysis of diplotypes derived from jlLEP-A2 SNPs revealed an association with growth traits in male but not female Jian carp. These results demonstrate that polymorphisms in the leptin gene are associated with growth traits and may be used for marker-assisted selection programs in Jian carp breeding and production.

Association of polymorphisms in growth hormone and leptin candidate genes with live weight traits of Brahman cattle.

Polymorphisms in candidate genes can produce significant and favorable changes in the phenotype, and therefore are useful for the identification of the best combination of favorable variants for marker-assisted selection. In the present study, an assessment to evaluate the effect of 11 single nucleotide polymorphisms (SNPs) in candidate genes on live weight traits of registered Brahman cattle was performed. Data from purebred bulls were used in this assessment. The dataset included birth (BW), weaning (WW), and yearling (YW) weights. A panel of 11 SNP markers, selected by their formerly reported or apparent direct and indirect association with live weight traits, was included in an assessment previously confirming their minimum allele frequency (<0.05). Live weights were adjusted BW (aBW), WW (aWW), and YW (aYW) using a generalized linear model, which included the fixed effects of herd and season of birth and the random effect of the sire and year of birth. An SNP in a growth hormone gene (GH4.1) was significantly related to aWW (P = 0.035) with an estimate substitution effect of 3.97 kg (P = 0.0210). In addition, a leptin SNP (LEPg.978) was significantly associated with aYW (P = 0.003) with an estimate substitution effect of 9.57 kg (P = 0.0007). The results suggest that markers GH4.1 and LEPg.978 can be considered as candidate loci for assisted genetic improvement programs in Mexican Brahman cattle.

Association of polymorphism in adiponectin (+45 T/G) and leptin (-2548 G/A) genes with type 2 diabetes mellitus in male Egyptians.

IntroductionAdiponectin is an adipose tissue-specific protein with insulin-sensitizing properties. Many investigators have explored the association between adiponectin single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) in different ethnic populations from different regions. Leptin is a protein hormone constituting an important signal in the regulation of adipose tissue mass and body weight. The aim of this study was to explore potential associations between SNP +45 T>G of the adiponectin gene and SNP 2548G/A of leptin with T2DM and the effect of SNPs on serum adiponectin and leptin levels.Material and methodsFrom the Egyptian population, we enrolled 110 T2DM patients and 90 non-diabetic controls. Serum lipid profile, blood glucose, serum adiponectin, and leptin were measured. Genotyping for two common SNPs of the adiponectin and leptin genes was performed by polymerase chain reaction–restriction fragment length polymorphism.ResultsThe G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compares to the controls. Subjects with the GG + TG genotype of SNP 45 were at increased risk for T2DM (OR = 6.476; 95% CI: 3.401–12.33) and associated with a low serum adiponectin level compared with the TT genotype. The serum leptin concentration of GA + AA genotype carriers was not significantly different from that of the GG genotype in the diabetic group.ConclusionsThe G allele carriers who have reduced plasma concentrations of adiponectin may have an association with T2DM, while leptin SNP 2548 G/A is not associated with the risk of development of T2DM in the Egyptian population.

The novel SNPs of leptin gene and their associations with growth traits in Chinese Nanjiang Yellow goat

The leptin (LEP) gene encodes a protein that greatly affects the regulation of body weight, energy balance, and food intake in mammals. The objective of the present work was to identify genetic variants of the caprine LEP gene in 411 individuals from five Chinese goat breeds. Six novel single nucleotide polymorphisms (SNPs) (g.117T>C, g.1642G>A, g.2883G>A, g.3053T>C, g.3190G>A, and g.3314T>C) were detected using DNA sequencing. A chi-squared (χ2) test showed that all of the LEP SNPs were in Hardy–Weinberg equilibrium in the studied population (P>0.05). Six common haplotypes were identified in the five goat populations, with frequencies ranging from 0.083 to 0.244. The r2 linkage disequilibrium plot of the LEP SNPs indicated linkage disequilibrium only in the cultured breeds (NJ and JY). Statistical analysis revealed that all of the six SNPs of the LEP gene were associated with growth traits. The individuals with the GG genotype at g.1642G>A and g.3190G>A loci showed higher birth weight (2.38±0.03, 2.43±0.05) and weight at 2months of age (10.59±0.16, 10.71±0.26) than the A-bearing genotypes (AA or GA, P<0.05). Our findings indicate that polymorphisms of the caprine LEP gene might be important genetic factors influencing growth traits, and these genetic markers may be useful for future marker-assisted selection programs in goat breeding and production.

PP.40.14

Objective: Resistant hypertension (RH) is a multifactorial and polygenic condition frequently associated with metabolic disorders such as obesity and diabetes. Leptin – a hormone produced by adipose tissue – has been related to the lack of blood pressure control as well as target organ damage in RH subjects. Moreover, single-nucleotide polymorphisms (SNPs) rs7799039 and rs1137101 in leptin (LEP) and leptin receptor (LEPR) coding genes, respectively, were associated with cardiovascular disease and metabolic syndrome. This study evaluated the association of these two SNPs -2548G/A and + 668A/G with clinical and biochemical features in RH subjects. Design and method: This cross-sectional study comprised 60 RH patients genotyped for both polymorphisms by Real-time Polymerase Chain Reaction method using fluorescent TaqMan probes. We compared GG (n = 46) vs. AA (n = 14) for rs7799039 and AA (n = 34) vs. GG (n = 26) genotypes for rs1137101. Leptin levels were measured by ELISA and bioimpedance estimated the body composition. Target organ damages were determined by echocardiography, pulse wave velocity (PWV) and microalbuminuria. Results: The both SNPs did not change leptin levels. On the other hand, LEP SNP modulated the levels of glycated hemoglobin (6.4 ± 1.4 vs.7.8 ± 2.3 %, p = 0.03), insulin (8.6 ± 4.6 vs. 30.6 ± 27.7 uUI/mL, p = 0.01), HDL-cholesterol (51 ± 16 vs. 39 ± 11 mg/dL, p = 0.001) and PWV (9.5 ± 2.1 vs. 11.2 ± 2.8 m/s, p = 0.03). As the same way, LEPR SNP modulated heart rate (69 ± 12 vs. 67 ± 12 bpm, p = 0.03), fat mass (31 ± 11 vs. 24 ± 8 Kg, p = 0.03) and triglycerides levels (175 ± 69 vs. 135 ± 75 mg/dL, p = 0.03). Conclusions: The -2548G/A and +668A/G modulated some clinical and biochemical traits in RH subjects, although were not associated with leptin levels.

The best anthropometric indices for predicting the incidence of hypertension

Resistant hypertension (RH) is a multifactorial and polygenic condition frequently associated with metabolic disorders such as obesity and diabetes. Leptin a hormone produced by adipose tissue has been related to the lack of blood pressure control as well as target organ damage in RH subjects. Moreover, single-nucleotide polymorphisms (SNPs) rs7799039 and rs1137101 in leptin (LEP) and leptin receptor (LEPR) coding genes, respectively, were associated with cardiovascular disease and metabolic syndrome. This study evaluated the association of these two SNPs -2548G/A and +668A/G with clinical and biochemical features in RH subjects. This cross-sectional study comprised 60 RH patients genotyped for both polymorphisms by Real-time Polymerase Chain Reaction method using fluorescent TaqMan probes. We compared GG (n1⁄446) vs. AA (n1⁄414) for rs7799039 and AA (n1⁄434) vs. GG (n1⁄426) genotypes for rs1137101. Leptin levels were measured by ELISA and bioimpedance estimated the body composition. Target organ damages were determined by echocardiography, pulse wave velocity (PWV) and microalbuminuria. The both SNPs did not change leptin levels. On the other hand, LEP SNP modulated the levels of glycated hemoglobin (6.4 1.4 vs.7.8 2.3 %, p1⁄40.03), insulin (8.6 4.6 vs. 30.6 27.7 uUI/mL, p1⁄40.01), HDLcholesterol (51 16 vs. 39 11 mg/dL, p1⁄40.001) and PWV (9.5 2.1 vs. 11.2 2.8 m/s, p1⁄40.03). As the same way, LEPR SNP modulated heart rate (69 12 vs. 67 12 bpm, p1⁄40.03), fat mass (31 11 vs. 24 8 Kg, p1⁄40.03) and triglycerides levels (175 69 vs. 135 75 mg/dL, p1⁄40.03). The -2548G/A and +668A/G modulated some clinical and biochemical traits in RH subjects, although were not associated with leptin levels.

Association of Genetic Polymorphisms of Leptin Receptor (LEPR) With New Onset Diabetes After Transplantation in Renal Transplantation.

BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a serious metabolic complication after renal transplantation. Leptin has an important role in the regulation of fat metabolism and glucose uptake. Although the links of insulin resistance and genetic variants at leptin (LEP) and leptin receptor gene (LEPR) were reported, relatively no studies have investigated the associations of PTDM. In this study, we investigated whether single nucleotide polymorphisms in LEP and LEPR have any association with PTDM in renal transplant recipients. METNODS: A total of 301 patients who had received kidney transplants without previously diagnosed diabetes were included. We analyzed the association between the PTDM development and the 5 SNPs within LEP and LEPR. RESULTS: Of 301 subjects, PTDM developed in 48 patients (15.9%). Patients in the PTDM group were older than those in the non-PTDM group. The sex ratio and BMI between two groups were similar. The percentage of steroid-treated acute rejection episodes and using tacrolimus were no significant different between the two groups. The patients with PTDM had significantly higher allele frequency of the LEPR rs1137100*G allele. We also observed significant higher distribution of A/A plus G/A genotypes of LEPR rs1137100 in PTDM subjects than in control subjects under a dominant model. Of four SNPs, the rs2167270 and rs13228377 of the LEP gene and the rs1327118 and rs3806318 of the LEPR were not significantly associated with the development of PTDM. CONCLUSION: Our data suggests that genetic variants of LEPR might have an essential role in the pathogenesis of PTDM.

Impact of a leptin single nucleotide polymorphism and ractopamine hydrochloride on growth and carcass characteristics in finishing steers.

A total of 2,958 steers (mean initial BW = 549.6 ± 3.88 kg) were used to test for the interactive effects, of leptin R25C genotypes (CC, CT, or TT) and feeding of ractopamine hydrochloride (RH) on growth performance and carcass traits. Before application of the drug, steers were blocked by arrival at the feed yard, genotyped for the leptin SNP, allotted to genotype-specific pens, and assigned randomly within genotype and block to 0 or 28 d of dietary RH. All pens within a block were slaughtered on the same day. Final BW of steers fed RH was 9.1 kg heavier (P < 0.001), and RH-fed steers had greater (P < 0.001) ADG and greater (P = 0.001) HCW than steers not fed RH. Feeding RH did not (P = 0.723) affect DMI but it did increase (P = 0.001) with increased frequency of the T allele (8.62, 8.70, and 8.82 kg/d for CC, CT, and TT, respectively). Consistent with the effect of leptin on DMI, increased frequency of the T allele also positively affected 12th rib fat (P = 0.001) and empty body fat (P = 0.001). Regardless of RH-feeding duration, TT steers produced a greater (P = 0.001) percentage of USDA yield grade (YG) 4 or higher carcasses (6.46 vs. 2.98%) and a lesser (P = 0.023) percentage of YG 1 carcasses (16.0 vs. 21.9%) than CC steers. In addition, RH-fed steers produced a lesser (P = 0.034) percentage of USDA YG 4 or higher carcasses (3.70 vs. 5.31%) and a lesser percentage (P = 0.019) of USDA Choice or higher carcasses (57.5 vs. 62.5%) than steers fed the control diet. Results indicated that leptin R25C genotype impacted most traits associated with fatness, whereas feeding RH for 28 d affected HCW and ADG positively but impacted marbling and USDA quality grades negatively.

Association between polymorphisms in leptin, leptin receptor, and β-adrenergic receptor genes and bone mineral density in postmenopausal Korean women

The purpose of this study was to investigate the association between single nucleotide polymorphisms in leptin (LEP), leptin receptor (LEPR), and β-adrenergic receptor (ADRB) genes and bone mineral density (BMD) in postmenopausal Korean women. LEP c.280G>A, LEPR c.326A>G, LEPR c.668A>G, LEPR c.1968G>C, LEPR c.2096C>T, ADRB2 c.46A>G, ADRB2 c.79C>G, ADRB2 c.718T>C, ADRB2 c.741G>T, ADRB2 c.769G>A, and ADRB3 c.190T>C polymorphisms were analyzed in 592 postmenopausal Korean women. Serum levels of leptin, soluble leptin receptor, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, bone alkaline phosphatase, and carboxy-terminal telopeptide of type I collagen were measured, and BMDs at the lumbar spine and femoral neck were also examined. Among the polymorphisms measured, only the LEPR c.1968G>C polymorphism was found to be associated with BMD at the femoral neck, and higher BMD was observed with increasing number of G alleles (P = 0.04). Osteoporosis at the femoral neck was 3.27 and 3.89 times more frequently observed in the AG and GG genotypes than in the AA genotype in the ADRB2 c.46A>G polymorphism (P = 0.024 and P = 0.015, respectively). However, no significant differences in serum levels of leptin, soluble leptin receptor, free leptin index, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, and bone turnover markers were detected among single and haplotype genotypes. These results suggest that the LEPR c.1968G>C polymorphism may be one of the genetic factors affecting femoral neck BMD in postmenopausal Korean women and that an analysis of the ADRB2 c.46A>G polymorphism may be useful in identifying women at risk for osteoporosis at the femoral neck.

Impact of a leptin single nucleotide polymorphism and zilpaterol hydrochloride on growth and carcass characteristics in finishing steers

A total of 4,178 steers (mean initial BW = 403.9 ± 16.04 kg) were used to test the interactive effects, if any, of leptin R25C genotypes (CC, CT, or TT) and zilpaterol hydrochloride (ZH) feeding duration on growth performance and carcass traits. Steers were blocked by arrival at the feed yard, genotyped for the leptin SNP, allotted to genotype-specific pens (90 steers/pen), and assigned randomly within genotype and block to 0 or 21 d of dietary ZH. All pens within a block were slaughtered on the same day (132.1 ± 10.9 d on feed). Final BW of steers fed ZH was 6.0 kg heavier (P = 0.008), and ZH-fed steers had greater (P = 0.003) ADG than steers not fed ZH. Feeding ZH decreased DMI in steers with increased frequency of the T allele (9.67, 9.53, and 9.28 kg/d for CC, CT, and TT, respectively), but DMI increased with the frequency of the T allele (9.68, 9.90, and 10.1 kg for CC, CT, and TT, respectively) when ZH was not fed (leptin genotype × ZH, P = 0.011). At the conclusion of the study, ultrasonic fat was greatest for TT steers (11.4 ± 0.28 mm) and least (P = 0.003) for CC steers (11.0 ± 0.25 mm). Regardless of ZH-feeding duration, TT steers produced a greater (P = 0.006) percentage of USDA yield grade (YG) 4 or higher carcasses (5.4 vs. 2.7%) and a lesser (P = 0.006) percentage of YG 1 carcasses (17.7 vs. 26.8%) than CC steers. In addition, ZH-fed steers produced a greater (P < 0.001) percentage of USDA YG 1 carcasses (25.9 vs. 16.2%) and a lesser (P < 0.001) percentage of YG 4 or higher carcasses (1.6 vs. 6.0%) than steers fed the control diet. Marbling scores and the percentage of carcasses grading USDA Choice and Prime were greater in TT than CC steers when fed diets devoid of ZH, but both marbling and quality grades did not differ among leptin genotypes when fed ZH for 21 d (leptin genotype × ZH, P ≤ 0.03). The amount of HCW gain tended to be less (P = 0.095) for steers of the TT genotype (12.7 kg) than either CC (16.3 kg) or CT (17.0 kg) genotypes. Results indicated that leptin R25C genotype impacted most traits associated with fatness whereas feeding ZH for 21 d affected HCW and ADG positively but impacted feed intake, marbling, and USDA quality grades negatively.