LEPR p.Q223R, beta3-AR p.W64R and LEP c.-2548G>A gene variants in obese Brazilian subjects

Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. The adrenergic receptor beta3 (beta3-AR), leptin (LEP) and leptin receptor (LEPR) genes have been intensively evaluated in the search of variants that could be related to obesity and its cardiometabolic complications. The results of most of these studies have been controversial. In the present study, we investigated the relationship of the beta3-AR p.W64R, LEP c.-2548G>A and LEPR p.Q223R gene variants with body mass index (BMI), in Brazilian subjects of different genetic backgrounds and ethnic origins. Two hundred obese patients (60 males, 140 females, BMI > or = 30 kg/m2) were screened and compared to 150 lean healthy subjects (63 males, 87 females, BMI < or = 24 kg/m2). Genomic DNA was extracted and amplified by polymerase chain reaction. Polymerase chain reaction products were digested with specific restriction enzymes and separated by electrophoresis. There was no significant difference in the genotype frequency of the beta3-AR p.W64R and the LEP c.-2548G>A polymorphisms, between lean and obese subjects. However, the genotype and allele frequencies of the LEPR p.Q223R variant were significantly different between the normal weight and obese groups. Haplotype analysis has shown an association between the G/G allelic combination of c.-2548G>A LEP and c.668A>G LEPR, in obese subjects. Our results suggest that genetic variability in the leptin receptor is associated with body weight regulation, the LEPR p.Q223R variant being related to BMI increase. The haplotype combination of LEP c.-2548G>A and LEPR p.Q223R variants was related to a 58% increase in obesity risk.     

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.     

G-2548A polymorphism of the leptin gene is correlated with extreme obesity in Taiwanese aborigines

We examined the genetic associations of the G-2548A polymorphism in the promoter of the leptin (LEP) gene and the Gln223Arg (Q223R) polymorphism of the leptin receptor (LEPR) gene with obesity. Two hundred twenty-six obese aboriginal subjects (BMI > or = 27 kg/m2) and 182 aboriginal subjects with normal weight (BMI < 25 kg/m2) participated in this study. The polymorphisms of LEP G-2548A and LEPR Q223R were genotyped by polymerase chain reaction/restriction fragment length polymorphism, and their anthropometric characteristics were measured. Levels of leptin, triglycerides, and cholesterol were measured after overnight fasting. We found that the frequencies of the LEP G/G homozygote (22.6%) with Mendelian recessive (chi2 = 7.89, p = 0.005) and codominant (chi2 = 7.93, p = 0.02) models to be higher in the extremely obese subjects (BMI > or = 35 kg/m2) than in normal weight subjects (6.9%) but not in moderately obese subjects (35 > BMI > or = 27 kg/m2). There was no difference in genotypic frequency of the LEPR Q223R polymorphism between the extreme obese and control groups. We suggest that the LEP -2548 G/G homozygote plays a genetic recessive role in the development of extreme obesity in Taiwanese aborigines.     

Associations among Lipids, Leptin, and Leptin Receptor Gene Gin223Arg Polymorphisms and Breast Cancer in China

We evaluated the relationship among the leptin receptor (LEPR) gene Gln223Arg polymorphism, body mass index (BMI), waist and hip circumference ratio (WHR), dietary structure, lifestyle, and other biomarkers with breast cancer and determined whether they could be effective for the prevention and treatment of breast cancer. The Gln223Arg polymorphisms in the LEPR gene were investigated in blood deoxyribonucleic acid (DNA) available for 240 breast cancer cases and 500 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Leptin, insulin were determined by enzyme-linked immunosorbent assays. We found that the serum levels of leptin, insulin, triglyceride (TG), free cholesterol (FCH), apolipoprotain (APO) A1, and BMI were significantly higher in breast cancer cases than the controls, while physical activity was clearly less in breast cancer cases (P < 0.02 approximately P < 0.001, respectively). Moreover, there were significant association between the Gln223Arg genotype and breast cancer risk; homozygotes for AA and heterozygotes for AG,AG + GG genotypes had been proved to increase the risk of breast cancer, and their corresponding odds ratio were 7.14 (95% confidence interval [CI] = 1.92-25.64), 1.33(95% CI = 1.03-2.70), and 2.04 (95% CI = 1.09-3.82). Interestingly, logistic regression analysis showed that LEPR gene Gln223Arg polymorphism and elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB increased the risk of developing breast cancer, respectively. And, it also suggested that LEPR gene Gln223Arg polymorphisms, elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB should play a major role in the development of breast cancer.     

The 223A>G polymorphism of the leptin receptor gene is associated with macroangiopathy in type 2 diabetes mellitus

To determine whether leptin receptor (LEPR) 223A>G polymorphism has an effect on the plasma leptin levels and the macroangiopathic complications in type 2 diabetes mellitus (T2DM). The genotypes and allelic frequencies of the LEPR 223A>G were examined with polymerase chain reaction and restriction fragment length polymorphism in 301 patients with T2DM and 172 unrelated healthy subjects. The plasma concentrations of leptin were determined in all subjects. The mean plasma leptin levels in the T2DM group were significantly higher than that of controls and the plasma levels of leptin were higher in diabetic patients with macroangiopathy than in patients without macroangiopathy (P < 0.05). The genotype (GG, AG and AA) distribution of 223A>G polymorphism was 58.3, 32.5, and 9.2% in diabetic patients with macroangiopathy, 75.3, 22.1, and 2.6% in patients without macroangiopathy, and 70.3, 27.5, 2.2% in controls respectively, a significant difference was found between diabetic patients with and without macroangiopathy (P < 0.05). The frequency of the allele A was higher in patients with macroangiopathy than in patients without macroangiopathy (25.6 vs. 16.3%; P < 0.05). Moreover, the plasma leptin levels were markedly higher in patients with AA genotype than those with AG or GG genotype in patients with macroangiopathy (P < 0.05). The LEPR 223A>G gene polymorphism associated with a predisposition to increased plasma leptin levels could constitute a useful predictive marker for diabetic macroangiopathy.     

Association of the Q223R polymorphism with age at menarche in the leptin receptor gene in humans

Although genetics clearly influences the onset of menarche, the association of age at menarche (AAM) with variants in genes related to energy homeostasis remains unexplored. Our aim was to analyze the relationship of the Q223R polymorphism in the leptin receptor gene (LEPR(Q223R)) with AAM in a population-based sample of healthy pubertal girls. The study included 338 Spanish girls aged between 11 and 17 yr. Data were collected on AAM. The Q223R polymorphism in LEPR was detected by TaqMan allelic discrimination assays. Girls carrying the RR genotype had a significantly younger AAM (11.5 yr) than those carrying the QR (11.9 yr) or QQ (12.0 yr) genotype (P < 0.05). Furthermore, we found a significantly higher frequency of the RR genotype in girls with an AAM of 11 yr or younger than in girls with an AAM older than 12 yr (23.9% vs. 7.8%, χ(2) = 11.17, P = 0.0008). Also, the RR genotype frequency in girls with an AAM between 11 and 12 yr was significantly higher than in girls with an AAM older than 12 yr (16.8% vs. 7.8%, χ(2) = 3.97, P = 0.0046). The Q223R polymorphism in the LEPR gene is associated with variations in AAM among Spanish girls, with the RR genotype being related to earlier onset.     

Multilocus analyses of seven candidate genes suggest interacting pathways for obesity-related traits in Brazilian populations

We investigated whether variants in major candidate genes for food intake and body weight regulation contribute to obesity-related traits under a multilocus perspective. We studied 375 Brazilian subjects from partially isolated African-derived populations (quilombos). Seven variants displaying conflicting results in previous reports and supposedly implicated in the susceptibility of obesity-related phenotypes were investigated: β2-adrenergic receptor (ADRB2) (Arg16Gly), insulin induced gene 2 (INSIG2) (rs7566605), leptin (LEP) (A19G), LEP receptor (LEPR) (Gln223Arg), perilipin (PLIN) (6209T > C), peroxisome proliferator-activated receptor-γ (PPARG) (Pro12Ala), and resistin (RETN) (-420 C > G). Regression models as well as generalized multifactor dimensionality reduction (GMDR) were employed to test the contribution of individual effects and higher-order interactions to BMI and waist-hip ratio (WHR) variation and risk of overweight/obesity. The best multilocus association signal identified in the quilombos was further examined in an independent sample of 334 Brazilian subjects of European ancestry. In quilombos, only the PPARG polymorphism displayed significant individual effects (WHR variation, P = 0.028). No association was observed either with the risk of overweight/obesity (BMI ≥ 25 kg/m2), risk of obesity alone (BMI ≥ 30 kg/m2) or BMI variation. However, GMDR analyses revealed an interaction between the LEPR and ADRB2 polymorphisms (P = 0.009) as well as a third-order effect involving the latter two variants plus INSIG2 (P = 0.034) with overweight/obesity. Assessment of the LEPR-ADRB2 interaction in the second sample indicated a marginally significant association (P = 0.0724), which was further verified to be limited to men (P = 0.0118). Together, our findings suggest evidence for a two-locus interaction between the LEPR Gln223Arg and ADRB2 Arg16Gly variants in the risk of overweight/obesity, and highlight further the importance of multilocus effects in the genetic component of obesity.     

Effect of LEPR Gln223Arg polymorphism on breast cancer risk in different ethnic populations: a meta-analysis

Leptin and leptin receptor have been implicated in processes leading to breast cancer initiation and progression. An A to G transition mutation in codon 223, in exon 6 of the leptin receptor gene (LEPR) can result in glutamine to arginine substitution (Gln223Arg). A variety of case–control studies have been published evaluating the association between LEPR Gln223Arg polymorphism and breast cancer. However, published studies have yielded contradictory conclusions. This meta-analysis enrolled eight studies to estimate the overall risk of LEPR Gln223Arg polymorphism associated with breast cancer. The pooled ORs were performed for codominant model (Arg/Arg versus Gln/Gln; Arg/Gln versus Gln/Gln), dominant model (Arg/Arg + Arg/Gln versus Gln/Gln), recessive model (Arg/Arg versus Arg/Gln + Gln/Gln). Overall significantly elevated breast cancer risk was found for recessive model (OR 1.32, 95% CI 1.03–1.69) and for genotype Arg/Gln versus Gln/Gln (OR 1.16, 95% CI 1.01–1.34). In the stratified analysis by ethnicity, significantly increased risks were also found among Africans for genotype Arg/Arg versus Gln/Gln: OR 1.86, 95% CI 1.28–2.71, Arg/Gln versus Gln/Gln: OR 1.48, 95% CI 1.10–1.99, dominant model: OR 1.60, 95% CI 1.21–2.11 and recessive model: OR 1.48, 95% CI 1.07–2.05; for Asians, Arg/Arg versus Gln/Gln: OR 6.79, 95% CI 3.42–13.47 and dominant model: OR 2.03, 95% CI 1.42–2.90. However, no significantly increased risk was found among Europeans for all genetic models. In conclusion, the LEPR 223Arg is a low-penetrant risk for developing breast cancer, especially for black African women.     

Leptin G-2548A and leptin receptor Q223R gene polymorphisms are not associated with obesity in Romanian subjects

We aimed to investigate whether polymorphisms LEP G-2548A and LEPR Q223R in the human leptin (LEP), and leptin receptor (LEPR) genes are associated with obesity and metabolic traits in a sample of Romanian population. Two hundred and two subjects divided in obese (body mass index, BMI ? 30 kg/m²), and non-obese were included in this study. The polymorphisms were genotyped using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. The results showed no significant differences in LEP and LEPR genotype and allele frequencies between obese and non-obese subjects. Logistic regression analysis showed that LEP -2548GG genotype presented an increased risk of obesity (p = 0.013, OR = 1.003, 95% CI = 1.000-1.007), after adjusting for age and gender. The association analysis with metabolic syndrome quantitative traits showed that homozygous for LEP -2548G allele had significantly higher leptin levels (17.2 ± 6.6 ng/ml vs. 13.2 ± 4.9 ng/ml, p = 0.011), and carriers of R allele had higher levels of triglycerides (p = 0.017) and glucose (p = 0.040), and enhanced systolic (p = 0.015) and diastolic blood pressure (p = 0.026), after adjustment for age, gender, and BMI. These results indicate that LEP G-2548A and LEPR Q223R SNPs may not be considered as genetic risk factors for obesity in a sample of Romanian population. However, LEP -2548GG genotype appear to be important in regulating leptin levels, whereas the LEPR 223R allele might predispose healthy subjects to develop metabolic disturbances.     

宁夏回族原发性膝骨性关节炎与瘦素受体基因多态性的相关性

为探讨宁夏回族原发性膝骨性关节炎(Osteoarthritis, OA)与瘦素受体基因(Leptin receptor, LEPR)A668G位点单核苷酸多态性(SNPs)之间的关系, 文章运用病例-对照研究, 通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术, 对148例兼具原发症状和影象证据的宁夏回族膝OA患者以及155名年龄、性别相匹配的对照群体进行LEPR A668G SNPs检测, 并进行测序验证, 分析LEPR基因多态性与膝OA的易感关联。研究表明, 膝OA组瘦素(Leptin, LEP)水平显著高于对照组(P<0.001), 血浆可溶性瘦素受体(sLEPR)水平较对照组明显降低(P<0.001), 膝OA组LEPR A668G位点AG/GA+GG基因型和G等位基因的分布频率和对照组存在差异(P=0.008和P=0.024)。研究结果提示, LEPR A668G位点的多态性可能与宁夏回族人群中膝OA易感性相关, 可以作为预测宁夏回族膝OA发病危险的遗传标记及早期防治的候选基因之一。     

Functional consequences of the human leptin receptor (LEPR) Q223R transversion

Perturbations in the functional integrity of the leptin axis are obvious candidates for mediation of altered adiposity. In a large number of genetic association studies in humans, the nonconservative LEPR Q223R allele has been inconsistently associated with adiposity. Subtle, long-term effects of such genetic variants can be obscured by effects of the environment and other confounders that render definitive inferences difficult to reach. We directly assessed the biological effects of this variant in 129P3/J mice segregating for the humanized Lepr allele at codon 223. No effects of this allele were detected on body weight, composition, or energy expenditure in animals fed diets of varying fat content over periods as long as 235 days. In vitro, Q223R did not affect leptin signaling as reflected by activation of STAT3. We conclude that Q223R is unlikely to play a significant role in regulation of human adiposity. This approach to vetting of human allelic variation might be more widely used.     

A missense mutation in the bovine leptin receptor gene is associated with leptin concentrations during late pregnancy

The leptin receptor (LEPR) gene consists of 20 exons divided over 1.75 Mb. Parts of bovine LEPR exon 4 (79 bp), exon 11 (95 bp) and exon 20 (513 bp) of 20 cows (Holstein-Friesian) were sequenced (AJ580799; AJ580800; AJ580801) in an attempt to find polymorphisms. In exons 4 and 11 no SNPs were found. In exon 20, a T to C missense mutation was found at nucleotide 115, which causes an amino acid substitution at residue 945 (T945M). Frequencies for alleles C and T were 0.93 and 0.07 respectively, in a population of 323 Holstein-Friesian cows and TT animals were not detected. Using genotypes of these cows an association study was performed for leptin concentrations during late pregnancy and lactation. Leptin concentrations were determined by radioimmunoassay (RIA). The T945M mutation showed an association with circulating leptin concentrations only during late pregnancy (P < 0.05) but not during lactation (P > 0.05). The CC genotype had higher concentrations than the CT genotype during this period. A combined effect with previously described leptin polymorphisms on prepartum leptin concentrations was observed, with one genotype combination having significantly lower levels of leptin up to 50 days, but interaction effects were not significant. The T945M polymorphism may have induced a structural change in the intracellular domain of the LEPR, which may have influenced the signal transduction pathway. However, the effect was found only for the heterozygous genotype because the TT genotype was not detected in this population of 323 Holstein-Friesian cows.     

瘦素受体基因Lys109Arg 多态性与慢性阻塞性肺疾病营养状况的关系

目的:探讨瘦素受体基因Lys109Arg多态性与慢性阻塞性肺疾病营养状况的关系。对象与方法:观察159例COPD稳定期患者及110例健康对照者体重指数(BMI)、理想体重百分比(NW%)、三头肌皮皱厚度(TSF)、上臂中点臂围(MAC)、血清白蛋白(ALB)、总淋巴细胞(LYM)等营养参数,将COPD组分为营养不良组(COPD1组)68例,COPD非营养不良组(COPD2组)91例。用酶联免疫吸附试验(ELISA)法测定血清瘦素水平,采用聚合酶链式反应及连接酶检测反应方法(PCR-LDR)测定瘦素受体Lysl09Arg多态性的基因型。结果:COPD1组Lys109Arg基因型GG、GA及AA的频率分别为0.838、0.147和0.015,G和A等位基因分别为0.912和0.088;COPD2组Lys109Arg基因型GG、GA及AA的频率分别为0.67、0.319和0.011,G和A等位基因分别为0.83和0.17;对照组Lys109Arg基因型GG、GA及AA的频率分别为0.7、0.273和0.027,G和A等位基因分别0.841和0.159;COPD1组Lys109Arg基因型及等位基因频率与COPD2组和对照组比较差异有显著性;COPD2组和对照组比较差异无显著性。GG型受试者血清瘦素水平低于A/G型+AA型(39.08±15.79ng/ml vs 43.29±17.25ng/ml),但差异无统计学意义。结论:瘦素受体基因Lys109Arg多态性可能与COPD营养状况相关。     

Pro-oxidant effect of α-tocopherol in patients with Type 2 Diabetes after an oral glucose tolerance test – a randomised controlled trial

Background

Little information is available on leptin concentrations in individuals with IGT. This study aims to determine and correlate leptin levels to anthropometric measures of obesity in pre-diabetic, (IFG and IGT), type 2 diabetic and normoglycaemic Saudis.

Methods

308 adult Saudis (healthy controls n = 80; pre-diabetes n = 86; Type 2 diabetes n = 142) participated. Anthropometric parameters were measured and fasting blood samples taken. Serum insulin was analysed, using a solid phase enzyme amplified sensitivity immunoassay and also leptin concentrations, using radio-immunoassay. The remaining blood parameters were determined using standard laboratory procedures.

Results

Leptin levels of diabetic and pre-diabetic men were higher than in normoglycaemic men (12.4 [3.2–72] vs 3.9 [0.8–20.0] ng/mL, (median [interquartile range], p = 0.0001). In females, leptin levels were significantly higher in pre-diabetic subjects (14.09 [2.8–44.4] ng/mL) than in normoglycaemic subjects (10.2 [0.25–34.8] ng/mL) (p = 0.046). After adjustment for BMI and gender, hip circumference was associated with log leptin (p = 0.006 with R2 = 0.086) among all subjects.

Conclusion

Leptin is associated with measures of adiposity, hip circumference in particular, in the non-diabetic state among Saudi subjects. The higher leptin level among diabetics and pre-diabetics is not related to differences in anthropometric measures of obesity.     

Spontaneous nocturnal leptin secretion in children with myelomeningocele and growth hormone deficiency

OBJECTIVE: To examine the spontaneous leptin secretion in patients with myelomeningocele (MMC) and growth hormone deficiency (GHD). METHODS: Serum leptin levels were studied in 10 prepubertal MMC patients with GHD (CA 6.2 +/- 0.5 years), 10 patients with idiopathic GHD (IGHD; CA 7.6 +/- 0.7 years) and 12 children with normal variant short stature (NVSS; CA 7.6 +/- 0.5 years). Mean BMI (kg/m(2)) values of the groups did not differ significantly. Nocturnal leptin levels were analyzed over 10 h (blood samples every 20 min) and measured by specific radioimmunoassay. RESULTS: Mean leptin concentrations did not correlate with BMI in MMC patients. Nocturnal leptin secretion of MMC patients was significantly different to those of children with IGHD and NVSS. Morning leptin levels did not decline as observed in both other groups. CONCLUSION: Since all groups were matched for BMI values, we suggest a hypothalamic dysregulation of leptin secretion in MMC patients.     

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

Background

This 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.

Methods

Convenience 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).

Results

The 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.

Conclusions

The 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.     

Association of leptin receptor gene Q223R polymorphism on lipid profiles in comparison study between obese and non-obese subjects

Objectives

Leptin is a hormone secreted from adipocytes. It regulates metabolism and energy homeostasis through the leptin receptor (LEPR) which is localized centrally in hypothalamus as well as in peripheral tissues. The aim of this study was to investigate the association of leptin receptor gene Q223R polymorphism on obesity in association with body mass index (BMI), lipid parameters, plasma leptin levels and homeostasis model assessment of insulin resistance (HOMA-IR).

Design and methods

The study included 110 obese and 90 non-obese subjects. The LEPR Q223R polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Plasma leptin levels, serum lipid and antropometric parameters were measured.

Results

No association was found between LEPR gene Q223R polymorphism and BMI in both study and control groups. Strikingly study group with non-obese subjects and with the RR genotype (homozygous mutant) had significantly higher serum total cholesterol (p < 0.001) and low density lipoprotein cholesterol (LDL-cholesterol) levels (p < 0.05) than QR (heterozygous) and QQ (wild type) genotypes. In obese group, subjects with the RR genotypes had significantly higher triglycerides (p < 0.05) levels, waist (p < 0.05) and hip circumferences (p < 0.001) than the QQ and QR genotypes.

Conclusions

Our results suggest that the LEPR gene Q223R polymorphism has an association with waist and hip circumferences in obese group but no direct association with obesity although there is a significant influence on lipid profile both in obese and non-obese subjects.     

Dynamic changes of orexin A and leptin in obese children during body weight reduction

In this study, we describe changes of plasma levels of the hypothalamic neuropeptide orexin A in obese children during the reduction of body weight and its relationship to other biochemical and anthropometrical parameters. We measured orexin A fasting plasma levels by the RIA method in 58 obese children--33 girls and 25 boys; mean age 13.1+/-0.38 years (range 7-18.5) before and after 5 weeks of weight-reduction therapy. Leptin, IGF-1, and IGFBP-3 levels were measured in all the subjects and were compared to orexin A levels and anthropometrical data. Average weight in subjects before weight-reduction was 74.2+/-2.79 kg and after weight-loss 67.4+/-2.60 kg (p<0.0001). Orexin A levels before the therapy were 33.3+/-1.97 pg/ml and after the therapy 51.7+/-3.07 pg/ml (p<0.0001). Levels of orexin A were not significantly different between girls and boys (p=0.7842). We found negative correlation between orexin A and age (r = -0.5395; p<0.0001), body height (r = -0.4751; p=0.0002), body weight (r = -0.4030; p=0.0017) and BMI (r = -0.2607; p=0.0481). No correlation was found between orexin A and IGF-1, IGFBP-3 or leptin. Orexin A plasma levels increased during body weight loss, whereas the reverse was true for leptin levels. These findings support the hypothesis that orexin A may be involved in regulation of nutritional status in children.     

Growth and anabolic hormones,leptin, and neuromuscular performance in moderately trained prepubescent athletes and untrained boys

We investigated hormonal regulators of growth and development, leptin levels, body composition, neuromuscular performance, and the associations among them in trained prepubertal athletes (experimental group [EG]) and an untrained control group (CG). Informed consent was obtained from the children and their parents. Their maturation stage was evaluated according to Tanner's criteria. There were no differences between EG and CG in physical characteristics, body mass index (BMI), lean body mass, testosterone (T), sex hormone-binding globulin, free androgen index, growth hormone (GH), hand grip strength, and jumping performance. Leptin levels and percent fat of the EG were significantly lower than those of the CG (p < 0.05-0.005). Leptin levels were significantly correlated to body fat and BMI for both the EG and the CG (r = 0.51-0.79). There is little evidence that leptin has a positive effect on growth and anabolic factors. Sex hormone-binding globulin and GH may explain the variation of leptin in athletes with low T (R(2) = 0.43) and in CG (R(2) = 0.35), respectively. Leptin seems to be a permissive factor for the onset of puberty, and the training background needs an optimal biological maturation to produce significant differences in muscle and power performance.