Effect of Trp64Arg mutation of the β3-adrenergic receptor gene and C161T substitution of the peroxisome proliferator activated receptor γ gene on obesity in Japanese children

OBJECTIVE: Obesity is a multifactorial syndrome influenced by both genetic and behavioral factors. Trp64Arg mutation of the beta3-adrenergic receptor (AR) gene and C161T substitution of the peroxisome proliferator-activated receptor (PPAR) gamma gene have been reported to be associated with obesity or lipid metabolism in adults. However, the effects of these mutations on children have not yet been clarified. For this reason, we studied the effects of Trp64Arg mutation of the beta3-AR gene and C161T substitution of the PPARgamma gene on obesity in Japanese children. SUBJECTS AND METHODS: In order to determine the effects of Trp64Arg mutation of the beta3-AR gene and C161T substitution of the PPARgamma gene on obesity in children, 105 obese Japanese children were screened by the polymerase chain reaction and restriction fragment-length polymorphism analysis. Plasma lipid, apolipo-protein (apo), glucose, insulin and leptin levels were also determined. RESULTS: Obese boys with Trp64Arg showed a higher obesity index and lower plasma levels of high-density lipoprotein cholesterol (HDL-C), apoA-I and apoA-II than those of them without the mutation. Obese boys with both mutations showed a higher plasma leptin level than those with only the beta3-AR gene mutation or PPARgamma gene mutation. No significant effect of these mutations was found in obese girls. CONCLUSION: All of these data suggest that Trp64Arg mutation of the beta3-AR gene might affect obesity and HDL metabolism in obese boys. In contrast, C161T mutation of the PPARgamma gene, by itself, is unlikely to influence obesity, lipid metabolism or plasma leptin levels.     

Association of Trp64Arg polymorphism of beta3-adrenergic receptor with insulin resistance in Polish children with obesity

AIM: To establish the influence of the Trp64Arg variant of the beta3-adrenergic receptor (Trp64Arg- beta3AR) on body mass index (BMI) and insulin resistance (IR) in obese children. METHODS: BMI, presence of the Trp64Arg mutation, plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT) and IR were determined in 60 obese and 33 normal weight children. RESULTS: The frequency of Trp64Arg was similar in normal weight and obese children. BMI, glucose and insulin concentrations during an OGTT in children with Trp64Argbeta3AR were not different from those with Trp64Trpbeta3AR. IR was confirmed in 42.8% of children with Trp64Argbeta3AR and in 45.6% of children with Trp64Trpbeta3AR (NS). CONCLUSIONS: 1. The similar frequency of the Trp64Argbeta3AR variant in normal weight and obese children suggests that it is not a susceptibility gene for obesity in Polish children. 2. The presence of the Trp64Argbeta3AR variant does not have an unfavourable influence on BMI, glucose or insulin concentrations during OGTT or on IR frequency in Polish obese children.     

Association of a mutation in the β3-adrenergic receptor gene with obesity and response to dietary intervention in Chinese children

This study aimed to determine whether the Trp64Arg mutation in the beta3-adrenergic receptor beta3-adr) gene is related to childhood obesity and the response to dietary intervention for obesity. The study included 311 healthy children aged 8-11 y selected at random from 4 primary schools in Beijing. Fasting insulin and lipids were measured and anthropometry was carried out for all samples. The mutation of the beta3-adr gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Forty-seven obese children were selected and divided into two groups. One group received dietary intervention (36 subjects); the other served as the control group (11 subjects). After 3 mo of dietary intervention, anthropometry was carried out again in 47 obese children. The frequency of the mutated allele was similar in 73 overweight and 238 normal-weight children (0.18 and 0.17, respectively). Adjusted for age and sex. there was no significant difference in body mass index (BMI) and the levels of fasting lipids and insulin between those with and without the mutation of the 311 children. However, after 3 mo of dietary intervention. increases in weight and BMI were significantly lower in obese children without the mutation than in the control group (2.41 +/- 0.56 vs 4.43 +/- 0.70. p < 0.05: 0.48 +/- 0.24 vs 1.55 +/- 0.35, p < 0.05. respectively), but the changes in weight and BMI in obese children with the mutation were similar to the results in the controls (4.32 +/- 0.69 vs 4.43 +/- 0.70; 1.47 +/- 0.32 vs 1.55 +/- 0.35). CONCLUSION: The Trp64Arg mutation of the beta3-adr gene may predict the result of dietary intervention in obese children to some extent, but it was not a major factor affecting weight in Chinese children.     

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目的 探讨β3-肾上腺素能受体基因(p3-AR)Trp64Arg变异与新疆哈萨克族儿童肥胖的相关性.方法 选取乌鲁木齐周边地区95例6-12岁哈萨克族学龄肥胖儿童及87名非肥胖儿童,用限制性片段长度多态性方法检测被调查儿童的基因型,生化方法检测血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A(ApoA)、载脂蛋白B(ApoB)水平,并测量身高、体重.结果 变异型等位基因(C)在被调查对象中出现的频率为0.194,其中男0.210,女0.160.肥胖儿童中变异等位基因(C)、Trp64Arg变异基因型的出现频率明显高于非肥胖者(P＜0.05).单纯性肥胖儿童与非肥胖儿童比较,血清TG、TC、LDL-C、ApoB水平均明显升高(P＜0.05).B3-AR不同基因型间血脂比较,差异无统计学意义(P>0.05).结论 哈萨克族学龄儿童中存在一定的B3-AR Trp64Arg变异,可能与哈萨克族儿童肥胖有关.     

Association of adrenergic receptor gene polymorphisms with adolescent obesity in Taiwan

Background: Polymorphisms of β2‐adrenergic receptor (ADRB2) and β3‐adrenergic receptor (ADRB3) have been reported to be associated with obesity in adults and adolescents, although study results have been controversial. The aim of the present study was to investigate the association of polymorphisms of ADRB2 (Arg16Gly, Gln27Glu) and ADRB3 (Trp64Arg) with adolescent obesity in Taiwan. Methods: A total of 559 adolescent volunteers with equal numbers female and male were enrolled. Participants were divided into two groups: obese (body mass index [BMI]≥ 95th percentile) and normal weight (BMI 15th–85th percentile). Genomic DNA was extracted from buccal mucosa cells and genotyped in TaqMan assays. Genotype results and clinical subject characteristics were analyzed. Results: Among the three ADRB polymorphisms, only Arg16Gly polymorphism was found to be significantly correlated with adolescent obesity, especially in girls. Girls with genotype Gly/Gly had a lower probability of obesity than those with genotypes Arg/Gly or Arg/Arg (P= 0.006; Arg/Gly: odds ratio [OR], 2.57, 95% confidence interval [95%CI]: 1.22–5.41; Arg/Arg: OR, 3.03, 95%CI: 1.50–6.12). Girls with genotype Gly/Gly had lower BMI than those with genotype Arg/Arg (P= 0.049). Obese adolescents with genotype Gly/Gly had a lower probability of hypertension than those with genotype Arg/Gly or Arg/Arg (P= 0.005). Conclusions: Arg16Gly polymorphism of ADRB2 was significantly associated with obesity in female adolescents, and those with the Gly/Gly genotype were associated with a lower possibility of obesity and lower BMI. This polymorphism was also associated with a lower probability of hypertension in obese adolescents. The other two polymorphisms of ADRB (Gln27Glu and Trp64Arg) were not associated with adolescent obesity in Taiwan.     

Sudden infant death: no evidence for linkage to common polymorphisms in the uncoupling protein-1 and the beta3-adrenergic receptor genes

Thermal stress has been postulated to play a major role in the aetiology of sudden infant death (SID). The human uncoupling protein-1 (UCP-1), expressed in brown adipose tissue dissipates the transmitochondrial proton gradient as heat and plays a central role in energy homeostasis and thermogenesis. A common Bcl I polymorphism in the promoter region of the UCP-1 gene is associated with reduced UCP-1 adipose tissue mRNA and obesity. In addition, a common sequence variation in the beta3-adrenergic receptor gene (beta3-AR), Trp64Arg, has been linked to a decreased resting metabolic rate. To determine whether the UCP-1 Bcl I polymorphism and/or the Trp64Arg variant of beta3-AR are associated with the occurrence of SID, we determined the allele frequencies of these polymorphisms in 53 Austrian SID victims and 54 controls by nested PCR and restriction digestion using DNA extracted from Guthrie cards. We found that the allele frequencies of both polymorphisms did not differ between the SID and control groups (0.65/0.35 versus 0.72/0.28 for UCP-1 Bcl I, and 0.89/0.11 versus 0.93/0.07 for beta3-AR Trp64Arg in SID victims versus controls, respectively). CONCLUSION: Our data do not support a major association between the occurrence of sudden infant death and two common functional polymorphisms in the human uncoupling protein-1 and beta3-adrenergic receptor genes.     

Clinical features of the metabolic syndrome in adolescents: minor role of the Trp64Arg beta3-adrenergic receptor gene variant

Obesity and hypertension are increasing medical problems in adolescents. We evaluated the association between being overweight-particularly abdominal fat-and having hypertension and assessed the contribution of the Trp64Arg beta3-adrenergic receptor gene variant. In a population-based study, we determined family history, anthropometric variables, and arterial blood pressure of 934 high school students, out of whom we selected 121 normotensive and 54 hypertensive students. Biochemical measurements included circulating renin and angiotensin-converting enzyme activities, leptin, glucose, insulin and lipid levels, and beta3-adrenergic receptor genotypes. We used Mann-Whitney U test, chi2-test, and Spearman rank-order correlation. In the total population, hypertension prevalence increased across the entire range of body mass index (BMI) percentiles. In the sample, hypertensive students showed higher BMI, waist-to-hip ratio, triglycerides, and insulin resistance and lower HDL-cholesterol than normotensive students did. Age- and sex-adjusted systolic arterial blood pressure was correlated with BMI, waist-to-hip ratio, insulin resistance, and leptin. Leptin was correlated with BMI and homeostasis model assessment method. We found no association among hypertension, BMI, and leptin levels with beta3-adrenergic receptor genotypes. Especially in girls, the waist-to-hip ratio was, however, suggestively higher in Arg64 variant carriers than in noncarriers, independent of hypertension. In fact, there was a significantly (p < 0.01) higher frequency of carriers of the Arg64 variant across the waist-to-hip ratio quartiles. In adolescents of European origin, hypertension is associated with an increased degree of obesity among other characteristics of the metabolic syndrome; the Trp64Arg variant of the beta3-adrenergic receptor gene may favor the central adiposity gain.     

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目的探讨肥胖儿童黑皮质素4受体(MC4R)的突变频率及其与临床生化指标改变的关系。方法浙江大学医学院附属儿童医院等单位于2004—2005年,对200例肥胖及100例正常体重儿童,利用PCR及基因测序技术进行MC4R基因筛查,同时对200例肥胖儿童进行生化检测和口服葡萄糖耐量试验。结果(1)200例肥胖儿童中检出杂合子错义突变、无义突变3例;100例对照组中未检出突变;Val103Ile基因多态性在两组中分别有6例、2例。肥胖组中发现了3个新的杂合子突变位点Val166Ile、Cys277Stop、Arg310Lys;肥胖组和对照组中同时检测到新的杂合子变异Leu23Arg。(2)MC4R突变组和非突变组的肥胖儿童BMI、ALT、AST、TG、CHO、WBI-SI比较均无统计学意义(P>0·05)。结论(1)首次在汉族儿童人群中发现了MC4R基因3个新的杂合子突变位点(Val166Ile、Cys277Stop、Arg310Lys)。(2)Leu23Arg可能是汉族人群MC4R的基因多态性。     

Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children

OBJECTIVE: To search for mutations in melanocortin pathway elements, that is, the melanocortin-4 receptor (MC4R ), agouti-related protein (AGRP ), and (alpha-melanocyte-stimulating hormone (alpha MSH ) genes in children with severe obesity. STUDY DESIGN: Direct sequencing of the MC4R encoding sequence and single-strand polymorphism conformation analysis of AGRP and alpha MSH genes were performed in 63 severely obese children. Polymerase chain reaction (PCR) assays of restriction fragment length polymorphism were used to assess the frequency of each newly discovered mutation in 283 non-obese control subjects. RESULTS: Four dominantly inherited, heterozygous, missense MC4R mutations (Val50Met, Ser58Cys, Ile102Ser, and Ile170Val) were identified in 4 unrelated children and none of the control subjects. Expression of the obese phenotype was variable in mutation-positive family members. Clinical and laboratory features were similar in the obese children with and without an MC4R mutation. Two polymorphisms were detected in the AGRP -encoding sequence (a silent mutation in exon 1 and Ala67Thr in exon 2), with similar frequencies in the obese and control groups. No mutations were found in the alpha MSH gene. CONCLUSIONS: MC4R mutations may be a non-negligible cause of severe obesity in children with variable expression and penetrance. Mutations in AGRP and alpha MSH genes were not among the causes of obesity in our population.     

Genetic factors and clinical significance of acanthosis nigricans in obese Japanese children and adolescents

AIM: To clarify the clinical significance of acanthosis nigricans (AN) and the association of gene polymorphisms in the ss2- and ss3-adrenergic receptors (B2ADR and B3ADR) in Japanese obese children and adolescents. METHODS: Seventy obese subjects (56 boys, 14 girls) from 5 to 19 y of age were examined as to clinical features. Genetic analyses were performed in 83 obese subjects (61 boys, 22 girls), 2 to 17 y of age. Typing of gene polymorphisms in B2ADR and B3ADR was achieved by polymerase chain reaction (PCR) of genomic DNA and restriction fragment-length polymorphism analysis (PCR-RFLP). RESULTS: The group with AN (n = 30) had higher values for percent overweight, BMI, waist circumference, fasting insulin, HOMA-R, leptin and PAI-1 than the AN-negative group (n = 40), but there were no significant differences in age, sex or percent body fat between the two groups. The prevalences of B2ADR Gly16 and B3ADR Arg64 were significantly higher in AN-positive (n = 26) than in AN-negative (n = 57) subjects. In addition, the AN frequency was significantly higher in the group with both Gly16 and Arg64 than in the group with neither of these alleles (55.6% vs 12.5%, p < 0.05). CONCLUSION: We demonstrate that AN is a useful clinical marker for the severity of obesity associated with a high BMI, and that B2ADR Gly16 and B3ADR Arg64 are associated synergistically with AN in obese children and adolescents.     

Prevalence of melanocortin 4 receptor (MC4R) mutations and polymorphismsin consecutively ascertained obese children and adolescents from a pediatric health care utilization population

BACKGROUND: The prevalence of childhood obesity is steadily increasing. Weight regulation and food intake are subject to complex regulatory mechanisms. The leptinergic-melanocortinergic system is known to be of major importance. AIM OF THE STUDY: Identification of mutations in the melanocortin 4 receptor gene (MC4R) and of phenotypic effects of detected mutations in German obese children and adolescents. Family specific and cardiovascular risk factors were also analysed. PATIENTS: Consecutive ascertainment of 90 obese children and adolescents with a medium BMI SDS of + 2.6, age range 3 to 16 years. METHODS: Mutation screen within the MC4R was carried out by denaturing high performance liquid chromatography (dHPLC) and re-sequencing of samples with aberrant dHPLC patterns. Eating behaviour and obesity-associated diseases within the families were evaluated by semi-structured interviews. Metabolic evaluation included: oral glucose tolerance test (OGTT, WHO criteria) for calculation of insulin resistance (Homeostasis Model Assessment, HOMA) and insulin sensitivity index (ISI), lipid panel for lipid status, blood pressure measurement and abdominal ultrasound. RESULTS: Three patients were heterozygous MC4R mutation carriers (Thr112Met, Ala175Thr and Gly181Asp). Gly181Asp leads to a complete loss of function; whereas Thr112Met and Ala175Thr lead to a reduced receptor function. The patients with heterozygous MC4R mutations had BMIs, cholesterol levels and waist to hip ratios (W/H) that did not differ from the rest of our study group. The overall occurrence of hypertriglyceridemia (34 %) and hypercholesterinemia (22 %) was correlated with the W/H-ratio. The overall incidence of impaired glucose tolerance was 12 %. In those with a normal glucose tolerance 68 % already had an increased HOMA (mean 3.12; reference value < 1.9) and decreased ISI (mean 4.3; reference value > 7.2). The patients with MC4R mutations had a normal glucose tolerance with similar HOMA and ISI values compared to the rest of the patients. Hypertension was found in 24 % of all cases and blood pressure was correlated with BMI (r+ 0.8). None of the patients with MC4R mutations were hypertensive. Leptin levels did not discriminate between patients with MC4R mutations and the other patients. Five patients harboured one of the MC4R polymorphisms (Val103Ile, Ile251Leu). These were phenotypically indistinguishable from the individuals without MC4R variants. CONCLUSION: We detected MC4R mutations (Thr112Met, Ala175Thr and Gly181Asp) in 3.3 % and MC4R polymorphisms (Val103Ile, Ile251Leu) in 5.5 % of the analysed obese children and adolescents, respectively. The patients with MC4R mutations did not show a higher metabolic risk compared to obese children and adolescents without mutations. However the total study group is prone to an increased risk for developing metabolic and cardiovascular diseases.     

汉族肥胖儿童黑皮质素4受体基因筛查

目的探讨肥胖儿童黑皮质素4受体(MC4R)的突变频率及其与临床生化指标改变的关系。 方法浙江大学医学院附属儿童医院等单位于2004—2005年,对200例肥胖及100例正常体重儿童,利用PCR及基因测序技术进行MC4R基因筛查,同时对200例肥胖儿童进行生化检测和口服葡萄糖耐量试验。 结果(1)200例肥胖儿童中检出杂合子错义突变、无义突变3例;100例对照组中未检出突变;Val103Ile基因多态性在两组中分别有6例、2例。肥胖组中发现了3个新的杂合子突变位点Val166Ile、Cys277Stop、Arg310Lys;肥胖组和对照组中同时检测到新的杂合子变异Leu23Arg。(2)MC4R突变组和非突变组的肥胖儿童BMI、ALT、AST、TG、CHO、WBISI比较均无统计学意义(P>0.05)。 结论(1)首次在汉族儿童人群中发现了MC4R基因3个新的杂合子突变位点(Val166Ile、Cys277Stop、Arg310Lys)。(2)Leu23Arg可能是汉族人群MC4R的基因多态性。     

黑皮素4受体与儿童肥胖

黑皮素4受体 (melanocortin 4 receptor,MC4R)基因突变是引起人类肥胖最常见的原因.MC4R是5种已被发现的黑皮素受体之一,位于18 号染色体,由单一外显子构成. 研究证实MC4R基因与体质量调节密切相关,其突变能导致青少年严重肥胖,与遗传性肥胖病密切相关.     

Mutational analysis of the pro-opiomelanocortin gene in French obese children led to the identification of a novel deleterious heterozygous mutation located in the alpha-melanocyte stimulating hormone domain

The pro-opiomelanocotin (POMC) plays a key role in body weight regulation, where its derived peptides mediate leptin action via the hypothalamic melanocortin 4 receptor (MC4R). The pathogenic effects of POMC mutations have been challenged in obesity. Our aim was to assess the relevance of POMC mutations in a cohort of French obese and nonobese children. Direct sequencing of the POMC gene was performed in 322 obese and 363 control unrelated children. Functional studies for the novel Phe144Leu mutation included the response to alpha-melanocyte stimulating hormone (alphaMSH) and a competitive binding assay. POMC mutations were identified in 3.72% of obese [95% confidence interval (CI): 1.66-5.80] and 2.20% of control (95% CI: 0.69-3.71) subjects. The novel mutation located in the alphaMSH region of the POMC gene (Phe144Leu) was found in one obese child and was transmitted by the obese father. Functional studies showed that MC4R activation in response to Leu144alphaMSH was almost completely abolished due to a dramatically altered binding of Leu144alphaMSH to MC4R. The frequency of POMC mutations is not significantly different between obese and control children in our cohort. The novel heterozygous mutation Phe144Leu leading to the absence of melanocortin signaling was associated with early-onset obesity suggesting its pathogenic role.     

肥胖儿童黑皮素4受体基因筛查和突变功能预测研究

目的 对肥胖儿童中黑皮素4 受体(MC4R)基因编码区进行突变位点筛查,研究其与肥胖相关指标的关系,并对突变可能造成的基因功能改变进行预测。方法 选择北京市160 例7~18 岁重度肥胖和100 例体重正常的儿童青少年,进行身体测量和血生化指标检测。使用PCR、单链构象多态性和测序方法进行MC4R基因编码区筛查。使用生物信息学网络数据库对筛出的突变进行功能预测。结果 肥胖儿童中筛出杂合子错义突变3 例(Val95Ile、Val166Ile、Val179Ala);在对照组中筛出杂合子错义突变1 例(Met218Thr);Val103Ile变异在肥胖组和对照组中分别有 7 例(4.4%)和6 例(6.0%)(P>0.05)。其中肥胖组中筛出的Val179Ala 为首次发现的杂合子突变。携带Val95Ile、Val166Ile 或Val179Ala 突变的3 例肥胖儿童与未携带这3 个突变的其他157 例肥胖儿童的BMI、体重、腰围、臀围、血脂指标、血糖和脂肪百分比的比较差异均无统计学意义(P>0.05)。对筛出的突变进行功能预测,发现上述5 个变异均可能对蛋白质功能产生影响。结论 在肥胖儿童MC4R 基因编码区共发现5 个变异,其中Val179Ala 为首次发现的新突变;功能预测发现这5 个变异均可能对蛋白质的功能造成影响。     

血管紧张素转化酶基因插入/缺失多态性及β3肾上腺素能受体基因Trp64Arg多态性对胎儿宫内发育及新生儿胰岛素敏感性的影响

目的 探讨血管紧张素转化酶(angiotensin converting enzyme,ACE)基因插入/缺失(insertion/deletion,I/D)多态性及B3-肾上腺素能受体(β3-adrenalgic receptor,β3-AR)基因Trp64Arg多态性对胎儿宫内发育和新牛儿胰岛素敏感性的影响.方法 将入选296例新生儿分为2组,适于胎龄儿组222例,小于胎龄儿组74例,于生后3d哺乳前检测血糖、胰岛素,计算HOMA-IR值评估胰岛素敏感性,应用PCR-RFLP方法分析β3-AR基因Trp64Arg多态性及ACE基因I/D多态性(202例),比较不同基因型组的孕周、出生体重、出生体重百分位及胰岛素敏感性,应用SPSS 10.0软件进行统计学处理.结果 小于胎龄儿组HOMA-IR值(Ln对数转换后)为0.217±0.367,高于适于胎龄儿组0.001±0.378,差异有统计学意义(P相似文献   

Impact of leptin and leptin‐receptor gene polymorphisms on serum lipids in Japanese obese children

Aim: Leptin is one of the factors affecting serum lipid profile. We investigated the association between serum lipids and leptin/leptin receptor (LEPR) gene polymorphisms in obese Japanese children. Methods: One hundred and thirty‐six obese children (99 males and 37 females, relative weight over than 20%) from 5 to 17 years of age were recruited from 10 institutes. Four known polymorphisms in leptin gene [(+19)A G, (?2548)G A, (?188)C A, (?633)C T] and four known polymorphisms in LEPR gene [Lys109Arg, Gln223Arg, Pro(G)1019Pro(A), Ser(T)343Ser(C)] were determined using polymerase chain reaction‐restriction fragment length polymorphism‐based analyses. Results: No associations were found between leptin gene polymorphisms and serum lipid profile. On the other hand, Lys109Arg and Ser343Ser polymorphism in LEPR gene, but not Gln223Arg or Pro1019Pro, had significant relationships with serum lipid profile; lower total and low‐density lipoprotein cholesterol levels in Arg109Arg homozygotes, and lower TG levels in Ser343Ser(C/C) homozygotes. In addition, LEPR gene also associated with relative weight; Arg109Arg homozygotes had higher relative weight and Ser343Ser(C/C) homozygotes had lower one. Conclusion: These results suggest that LEPR gene polymorphisms may partly contribute to serum lipid profile in obese children.     

Leptin receptor gene Gln223Arg polymorphism is not associated with obesity and metabolic syndrome in Turkish children

The aim of the study was to investigate the relationship between leptin receptor gene (LEPR) Gln223Arg polymorphism and obesity in Turkish children. Ninety-two obese and 99 lean children (between 5-15 years) were included in the study. Twenty-three of the obese children were diagnosed with metabolic syndrome. Blood samples were collected for morning fasting blood glucose, insulin, leptin, and lipid level measurements. LEPR Gln223Arg polymorphism was analyzed by restriction fragment length polymorphism. Significant differences were observed in anthropometric measurements, fasting blood glucose, insulin, leptin, and lipid levels between obese and lean children. Serum leptin levels were markedly higher in obese children. No significant association was noted between Gln223Arg polymorphism and serum leptin, insulin and lipid levels. There were no differences in the genotype frequencies or allele distribution for Gln223Arg polymorphism among obese, obese with metabolic syndrome and lean children. Our findings suggest that there is no association between Gln223Arg polymorphism and obesity in Turkish children.     

Childhood obesity. Medical and familial correlates and age of onset

The prevalence of obesity in U.S. children is rising. Etiologic studies have focused on infants and school age children but little is known about obesity in early childhood. To study the development of childhood obesity and its medical correlates, the authors reviewed 175 charts of obese children seen in a nutrition clinic. The 61 study subjects (37% of charts reviewed) had growth records for ages 7 years and less and were without developmental delay syndromes. Thirty-nine (64%) of 61, were girls; ages at presentation were 1 to 14 years. Data collection included previous and presenting weights, heights, medical problems, and evidence of parental and sibling obesity. Study subjects' mean percent of ideal body weight for height (% IBWH) at presentation was 160 percent. Many study subjects had medical problems considered to be related to obesity: 30 percent had asthma, 25 percent elevated blood pressure, and 28 percent hyperlipidemia. Thirty (63%) of 48, study subjects with data on maternal weight and height, had obese mothers and 14 (31%) of 45 had obese fathers. Fourteen (50%) of 28 had one or more obese siblings. Among all study subjects, the proportion of obese (% IBWH greater than 120%) and severely obese children (% IBWH greater than 140%) increased between ages 1 and 7 years. For example, the proportion greater than 140% IBWH was zero percent at 1 year and 3 years; 0.1 at 2 years; 0.2 at 4 years; 0.5 at 5 to 6 years; and 0.6 at 7 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Childhood obesity: trends and potential causes

The increase in childhood obesity over the past several decades, together with the associated health problems and costs, is raising grave concern among health care professionals, policy experts, children's advocates, and parents. Patricia Anderson and Kristin Butcher document trends in children's obesity and examine the possible underlying causes of the obesity epidemic. They begin by reviewing research on energy intake, energy expenditure, and "energy balance," noting that children who eat more "empty calories" and expend fewer calories through physical activity are more likely to be obese than other children. Next they ask what has changed in children's environment over the past three decades to upset this energy balance equation. In particular, they examine changes in the food market, in the built environment, in schools and child care settings, and in the role of parents-paying attention to the timing of these changes. Among the changes that affect children's energy intake are the increasing availability of energy-dense, high-calorie foods and drinks through schools. Changes in the family, particularly an increase in dual-career or single-parent working families, may also have increased demand for food away from home or pre-prepared foods. A host of factors have also contributed to reductions in energy expenditure. In particular, children today seem less likely to walk to school and to be traveling more in cars than they were during the early 1970s, perhaps because of changes in the built environment. Finally, children spend more time viewing television and using computers. Anderson and Butcher find no one factor that has led to increases in children's obesity. Rather, many complementary changes have simultaneously increased children's energy intake and decreased their energy expenditure. The challenge in formulating policies to address children's obesity is to learn how best to change the environment that affects children's energy balance.