Genetics of obesity: an overview of current approaches and advancement.

Elucidation of obesity susceptibility genes through genome wide approaches as well as candidate gene approaches provides great promise in ultimately determining the genetic underpinnings of obesity. The complex nature of human obesity stems from the multiple interaction of several genes that control the physiology of food intake, energy expenditure, development of the body, and behavioural patterns towards food intake, and the environment. According to twin, adoptees and family studies, genetic factors account for 40-70% of the variability observed in human adiposity. Twin studies supported that the heritability of adiposity is higher than other quantitative traits. The heritability of obesity traits has been further evidenced by identification of quantitative trait loci (QTL) and genes through methods such as genome-wide scans (studies conducted on unrelated obese individuals), linkage analyses (conducted in families), and association studies (investigating the correlation between obesity and polymorphisms). The number of contributing genes, however, is still unknown. Although research on the genetic basis of obesity has advanced, the mechanisms underlying the condition are still complex due to its heterogeneity even within families.

Association between polymorphism of leptin receptor gene and serum leptin in asthma / 中国综合临床

Objective To investigate the relationship between leptin receptor(LEPR) gene Gln223Arg in polymorphism and serum leptin level of patients with asthma.Methods A case-control study was conducted.One hundred and ninety-two asthma patients were recruited from asthma gene library,among them 100 patients only with asthma(asthma group) and 92 patients with both asthma and metabolic syndrome(asthma complicated with metabolic syndrome group).And 108 normal people were selected as control group.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the polymorphism of LEPR gene Gln223Arg locus.Serum leptin levels were measured by enzyme-linked immuno sorbent assay,its relationship with asthma was analyze.Results The frequencies of genotype GG,GA,AA in asthma group,asthma complicated with metabolic syndrome group and normal control group were (83.00％ (83/100) vs.83.70％ (77/92) vs.70.37％ (76/108),15.00％ (15/100) vs.15.22％ (14/92) vs.27.78％ (30/108),and2.00％ (2/100) vs.1.08％ (1/92) vs.1.85％ (2/108) respectively).G and A alleles in asthma group,asthma complicated with metabolic syndrome group and normal control group were 90.50％ vs.91.30％vs.84.26％,9.50％ vs.8.70％ vs.15.74％ respectively.Compared with the control group,GG genotype and GA + AA genotype were different between in asthma group and asthma complicated with metabolic syndrome group.The patients with GG genotype showed 2.056 (x2 =4.599,P =0.032,OR =2.056,95％ CI =1.057-3.999) and 2.161 folds (x2 =4.907,P =0.027,OR =2.161,95 ％ CI =1.084-4.311) risk in asthma group and asthma complicated with metabolic syndrome group than that with GA + AA genotype.In terms of leptin levels,in asthma group,female were significant higher than that of control group (P =0.037,P =2.93),while in asthma complicated with metabolic syndrome group,male and female were significantly higher than control group (P =0.001,0.000 ; P =4.530,4.690).Conclusion The polymorphisms of LEPR gene locus Gln223 Arg are related with asthma.Genotype GG carrier is susceptible for the disease.In female,serum leptin is positive relationship with asthma group,especially in asthma complicated with metabolic syndrome.

Lack of mutations in the leptin receptor gene in severely obese children / Ausência de mutação no gene receptor de leptina em crianças gravemente obesas

OBJECTIVE: To analyze the LEPR gene in obese children and to investigate the associations between molecular findings and anthropometric and metabolic features. SUBJECTS AND METHODS: Thirty-two patients were evaluated regarding anthropometric characteristics, blood pressure, heart rate, serum glucose, insulin, leptin levels, and lipid profile. The molecular study consisted of the amplification and automatic sequencing of the coding region of LEPR in order to investigate new mutations. RESULTS: We identified a high prevalence of metabolic disorders: impaired fasting glucose in 12.5% of the patients, elevated HOMA-IR in 85.7%, low HDL-cholesterol levels in 46.9%, high triglyceride levels in 40.6%, and hypertension in 58.6% of the patients. The molecular study identified 6 already described allelic variants: rs1137100 (exon-2), rs1137101 (exon-4), rs1805134 (exon-7), rs8179183 (exon-12), rs1805096 (exon-18), and the deletion/insertion of the pentanucleotide CTTTA at 3'untranslated region. CONCLUSIONS: The frequency of alleles observed in this cohort is similar to that described in the literature, and was not correlated with any clinical feature. The molecular findings in the analysis of the LEPR did not seem to be implicated in the etiology of obesity in these patients.

OBJETIVO: Analisar o LEPR em crianças obesas e investigar associações entre achados moleculares e características antropométricas e metabólicas. SUJEITOS E MÉTODOS: Foram avaliados 32 pacientes quanto às características antropométricas, à pressão arterial, à frequência cardíaca, às dosagens séricas de glicemia, à insulina, à leptina e ao perfil lipídico. O estudo molecular consistiu na amplificação e no sequenciamento automático da região codificadora do LEPR para pesquisar mutações. RESULTADOS: Identificou-se uma alta prevalência de distúrbios metabólicos: glicemia de jejum alterada em 12,5%, HOMA-IR elevado em 85,7%, níveis de HDL-colesterol baixos em 46,9%, níveis de triglicérides elevados em 40,6% e hipertensão arterial em 58,6%. O estudo molecular identificou 6 variações alélicas já descritas na literatura: rs1137100 (éxon-2), rs1137101 (éxon-4), rs1805134 (éxon-7), rs8179183 (éxon-12), rs1805096 (éxon-18) e deleção/inserção do pentanucleotídeo CTTTA na região 3' não traduzida. CONCLUSÕES: A frequência das variações alélicas observada é semelhante à descrita na literatura e não se correlacionou com nenhuma característica clínica. Os resultados da análise molecular do LEPR não parecem estar implicados na etiologia da obesidade desses pacientes.

Effects of polymorphisms of leptin receptor gene 3057 G/A on serum leptin level of senile depressive patients / 中华行为医学与脑科学杂志

Objective To investigate the relation of serum leptin level in senile depressive patients with type 2 diabetes and polymorphisms of leptin receptor gene 3057 G/A.Methods 10 senile depressive patients with type 2 diabetes and 47 senile depressive patients without type 2 diabetes were selected for the study.Leptin levels were determined by radioimmunoassay.Genomitic DNA were obtained by phenol/chloroform method.Leptin receptor gene 3057 G/A polymorphisms and allele frequencies were determined with the polymerase chain reaction and restricted fragment length polymorphism assay.Results (1) The differences of leptin receptor genotypes and allele distribution in the 3 groups were not found (all P ＞ 0.05).(2) Serum leptin level in senile depressive patients with type 2 diabetes and without type 2 diabetic patients ((41.65 ± 28.19) ng/ml,(25.56 ± 21.04) ng/ml) were significantly higher than the normal people ((10.84 ± 9.16) ng/ml) (all P ＜ 0.05).Serum leptin level in senile depressive patients with type 2 diabetes were significantly higher than without type 2 diabetic patients(P＜ 0.05).(3) The serum leptin level in genotype AA senile depressive patients with type 2 diabetes were significantly higher than genotype AA patients without type 2 diabetes.The differences of the serum leptin levels in genotype AA senile depressive patients without type 2 diabetes and genotype AG/GG patients without type 2 diabetes were not found(P ＞ 0.05).The differences of the serum leptin level in genotype AA and genotype AG/GG in normal groups were not found (P＞ 0.05).Conclusion Senile depressive patients have higher serum leptin level.The serum leptin level is higher,especially with type 2 diabetes.Serum leptin level is related to type 2 diabetes.Serum leptin level is not related to the polymorphisms of leptin receptor gene 3057 G/A.Type 2 diabetes are not related to polymorphisms of leptin receptor gene 3057 G/A.

Relationship between the mutation of the exon 4 of leptin receptor gene and left ventrtcular function and renal hemodynamics in patients with hypertension / 中国医师进修杂志

Objective To investigate the relationship between the mutation of the exon 4 of leptin receptor gene(4Lys 109 Arg)and left ventricular function and renal hemodynamics in patients with hypertension.Methods From December 2005 to December 2006,digoxin marked primer enzyme coloration technique was used to detect the 4Lys 109 Arg polymorphism.The color Doppler echocardiography was used to detect the left ventricular function and the renal hemodynamics.The study covered 90 patients with hypertension (hypertension group)and 52 controls (control group).Results The frequencies of 4Lys109Arg in hypertension group and control group had no significant difference.The hypertension with GG genotype was significant difference in left ventrieular ejection fraction(LVEF),E/A,left ventrieular fractional shortening(LVFS),resistance index(BI),pulsatility index(PI)(P<0.05).The hypertension with GA genotype had significant difference in LVEF,E/A,LVFS(P<0.05).In hypertension group,LVEF,E/A,LVFS.RI and PI had significant difference between GG and AA genotype(P<0.05).In control goup,RI had significant difference between GG and AA genotype(0.65 ±0.02 vs 0.63±0.02,P<0.05).Conclusion The renal hemodynamics and the left ventricular function are associated with 4Lys109Arg polymorphism.

Association study of LEP and LEPR gene polymorphisms and the development of type 2 diabetes mellitus in Korean women with a history of gestational diabetes / 대한산부인과학회지

OBJECTIVE: The history of gestational diabetes (GDM) is a high risk for the development of type 2 diabetes mellitus (T2DM). The purpose of this study is to investigate the genetic association of LEP and LEPR gene polymorphisms and the development of T2DM in Korean women of history of GDM. METHODS: Women diagnosed as GDM during pregnancy from January 1992 to December 2002 were recruited. Those women with a T2DM at the time of study were classified as T2DM positive group, and without T2DM, as T2DM negative group. 2 genes (LEP and LEPR genes) and 8 SNPs (LEP-632G>A, +4950G>A, +4998A>C, and LEPR-141013T>C, -186A>G, +5193G>A, +7187A>C, +27265A>G) were selected. The TaqMan assay for genotyping and the statistical analysis for phenotypic and genetic factors between 2 groups were analyzed. RESULTS: A total of 54 women, T2DM positive (n=20) and T2DM negative (n=34) were enrolled. At the time of diagnosis of GDM, HbA1c, 50 g and 100 g oral glucose tolerance test, and insulin level were significantly associated between T2DM positive and negative groups (P<.05). In analysis of genetic risk to T2DM, the significant association related with any SNPs was not shown between T2DM positive and negative groups. CONCLUSION: In Korean women having past history of GDM, there was no relationship between 2 genes and the development to T2DM. To clarify a effect of candidate genes related with development of T2DM, there will need more samples and genes.

Variation of the human leptin receptor gene in obese Chinese population / 中华内分泌代谢杂志

Objective To investigate the relationship between the genetic variation of leptin receptor and obesity in Chinese population. Methods Genomic DNA was extracted from 50 obese subjects 〔Body mass index (BMI)≥30 kg/m 2〕 and 50 normal individuals (BMI