Type 2 diabetes is characterized by insulin resistance, and ENPP1 plays an important role in insulin resistance. We investigated the association of the ENPP1 K121Q polymorphism with both diabetes and obesity (body mass index [BMI]) in Korean male workers. The study design was case-control. Subjects were 1,945 male workers (type 2 diabetes, 195; non-diabetes, 1,750) of nuclear power plants who received examinations from March to October in 2004. We collected venous blood samples under fasting (> or =8 hr) conditions, calculated BMI by height and weight, and assessed relevant biochemical factors. The results of this study demonstrated that the ENPP1 121Q genotype (KQ+QQ types) was not associated with type 2 diabetes (odds ratios [OR], 0.854; 95% confidence interval [CI], 0.571-1.278) or obesity (OR, 0.933; 95% CI, 0.731-1.190). In addition, the frequency of the Q allele was not related to type 2 diabetes (OR, 0.911; 95% CI, 0.630-1.319) or obesity (OR, 0.962; 95% CI, 0.767-1.205). We concluded that the ENPP1 121Q allele is not a critical determinant for either diabetes or obesity in Korean males. The discordance between the results of this study and those derived from studies of Dominican, South Asian, Caucasian, Finnish, and French populations might be due to differences in genetic backgrounds between these populations.
Adult ; Diabetes Mellitus, Type 2/*ethnology/*genetics ; Employment ; Gene Frequency ; Genetic Predisposition to Disease/ethnology ; Genotype ; Humans ; Korea/epidemiology ; Male ; Middle Aged ; Obesity/*ethnology/*genetics ; Phosphoric Diester Hydrolases/*genetics ; Polymorphism, Genetic ; Prevalence ; Pyrophosphatases/*genetics

OBJECTIVETo investigate the relationship of leptin gene polymorphism with obesity in ethnic minority Hui and Uygur children in China.

METHODSSixty-eight ethnic minority (35 Hui and 33 Uygur) children with obesity and 69 age-matched minority (36 Hui and 33 Uygur) children without obesity were recruited from six primary schools in the sub-urban areas of Urumqi. Venous blood was sampled from all subjects after fasting for 12 hours. Leptin gene C2549A polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism methods. Blood concentrations of lipids, leptin and insulin were measured with biochemical methods and radioimmunoassys, respectively.

RESULTSIn the 137 children tested, the prevalence of AA, AC and CC genotype was 9.5%, 33.6% and 56.9%, respectively. A allele frequency was significantly different between the two ethnic (i.e. Hui and Uygur) groups (P<0.05). A allele frequency and AA+ AC genotype frequency were not significantly different between obese and non-obese children in both ethnic groups (P>0.05). Blood leptin levels were not significantly different between obese and non-obese children with an AA+AC or CC genotype in both ethnic groups (P>0.05).

CONCLUSIONSLeptin gene polymorphisms exist in Hui and Uygur children. The C2549A polymorphism is not significantly associated with the prevalence of obesity in both Hui and Uygur children.

Child ; China ; ethnology ; Female ; Genotype ; Humans ; Leptin ; blood ; genetics ; Lipids ; blood ; Male ; Obesity ; blood ; genetics ; Polymorphism, Genetic

OBJECTIVETo study the association between the rs7566605 variant of INSIG2 and obesity-related phenotypes in Chinese children and adolescents.

METHODSThe study sample consisted of two independent cohorts of Chinese children and adolescents. Anthropometric indices, lipids, blood pressure, fasting glucose, insulin and percentage of fat mass were determined. PCR with restriction fragment length polymorphism analysis was performed for genotyping the rs7566605 variant.

RESULTSIn each of the two independent cohorts, no significant association was observed between rs7566605 and obesity under additive, dominant or recessive model. We also did not detect any difference in the genotype frequency between all the obese children and controls. Furthermore, we did not find evidence of an association between body composition indices and metabolic phenotypes in all children. However, the triglyceride level of CC homozygotes was significantly higher than that of GG+GC genotypes in obese children (P=0.022). Additionally, we observed a non-significant trend of severe obesity in a post-hoc test.

CONCLUSIONINSIG2 rs7566605 variant is not associated Chinese childhood obesity in two independent cohorts. Further study is needed to verify the effect of rs7566605 on triglyceride in obese children.

Adipose Tissue ; Adolescent ; Asian Continental Ancestry Group ; ethnology ; genetics ; Body Mass Index ; Child ; China ; Cohort Studies ; Female ; Genetic Variation ; genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Membrane Proteins ; genetics ; Obesity ; ethnology ; genetics ; Phenotype ; Risk Factors ; Young Adult

OBJECTIVETo study the association between the prevalence of overweight/obesity and copy number variations (CNVs) among Han, Uyghur, and Kazak children in Xinjiang, China.

METHODSThe kindergartens in Ili, Altay, and Karamay in Xinjiang were selected as research sites, and stratified cluster sampling was used to select the children aged 3-7 years. Body height and body weight were measured, and exfoliated buccal mucosa cells were collected. CNVplex® was used to measure the CNVs of FTO_1, IRX3_1, IRX3_2, MC4R_1, and MC4R_2.

RESULTSA total of 603 children were surveyed (307 boys and 296 girls). There were 261 Han children, 194 Uyghur children, and 148 Kazak children. The overweight/obesity rates in Han, Uyghur, and Kazak children were 28.3%, 10.3%, and 31.1%, respectively (P<0.001). In Kazak children, the CNVs of IRX3_1 and MC4R_2 were associated with overweight/obesity (P<0.05). The multivariate logistic regression analysis showed that the risk of overweight/obesity in Han and Kazak children was 3.443 times (95%CI: 2.016-5.880) and 3.924 times (95%CI: 2.199-7.001), respectively, that in Uyghur children. The CNV of IRX3_1 was a risk factor for overweight/obesity (P=0.028, OR=2.251, 95%CI: 1.418-5.651).

CONCLUSIONSThe CNV of IRX3_1 is associated with overweight/obesity in Han, Uyghur, and Kazak children, and the association between the CNV of IRX3_1 and overweight/obesity in Kazak children should be taken seriously.

Child ; Child, Preschool ; China ; ethnology ; DNA Copy Number Variations ; Female ; Homeodomain Proteins ; genetics ; Humans ; Logistic Models ; Male ; Obesity ; etiology ; genetics ; Overweight ; etiology ; genetics ; Risk Factors ; Transcription Factors ; genetics

OBJECTIVETo investigate the -3826A/G polymorphism in the promoter of the uncoupling protein-1 (UCP1) gene and its relations to obesity in Chinese population.

METHODSThree hundred and eighty-four subjects (257 non-obese and 127 obese individuals) from a population of Chinese Han nationality in Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs). Serum lipids were measured by enzymatic kits and apolipoproteins A I, A II, B100, C II, C III and E were measured by the RID kits.

RESULTSThe frequencies of A and G alleles at -3826A/G site in obese and non-obese groups were 0.508 and 0.492, and 0.467 and 0.533, respectively. It showed no significant difference in allele frequencies between non-obese and obese groups (P > 0.05). In the obese group, subjects with genotype GG had higher serum apo B100 concentrations, and those with genotype AG had higher apo C II and apo C III levels, than those with genotype AA, respectively (P < 0.05). In non-obese male subgroup, subjects with genotype GG had lower serum HDL-C and apo A I levels than those with genotype AA, respectively (P < 0.05), whereas those with genotype AG had lower apo A II levels than those with genotype AA. In addition, in obese males with genotype GG had elevated apo B100 levels compared with those with genotype AA, whereas in obese females with genotype GG had decreased apo AI levels and genotype AG had increased apo C II and apo C III levels compared with those with genotype AG and AA, respectively (P < 0.05).

CONCLUSION-3826A/G polymorphism in the promoter of the uncoupling protein-1 gene was not associated with obesity in Chinese Han population of Chengdu area. It may be associated with serum HDL-C, apo A I and apo B100 levels in non-obese and/or obese subjects of certain genders.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Case-Control Studies ; Female ; Humans ; Ion Channels ; genetics ; Lipids ; blood ; Male ; Middle Aged ; Mitochondrial Proteins ; genetics ; Obesity ; blood ; ethnology ; genetics ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Uncoupling Protein 1

Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.
Adenocarcinoma ; ethnology ; etiology ; genetics ; Alcohol Drinking ; adverse effects ; Asia ; epidemiology ; Asian Continental Ancestry Group ; genetics ; Carcinoma, Squamous Cell ; ethnology ; etiology ; genetics ; Esophageal Neoplasms ; ethnology ; etiology ; genetics ; European Continental Ancestry Group ; genetics ; Gastroesophageal Reflux ; complications ; Genetic Predisposition to Disease ; Humans ; Incidence ; Obesity ; complications ; Polymorphism, Single Nucleotide ; Risk Factors ; Smoking ; adverse effects ; United States ; epidemiology

OBJECTIVETo study the association of rs9939609 polymorphism of the fat mass and obesity associated gene (FTO) with overweight or obesity in Hazakh children.

METHODSPCR-restriction fragment length polymorphism was used to determine the rs9939609 polymorphism in 141 patients with overweight or obesity and 138 healthy controls. Height and weight were measured for body mass index (BMI). Serum lipid levels including total cholesterol, triglyceride, high-density and low-density lipoprotein cholesterol, blood pressure, plasma glucose levels, and plasma insulin were also determined.

RESULTSThe genotype distributions of both groups were in the Hardy-Weinberg equilibrium. The frequencies of AA, AT and TT were 0.071, 0.511 and 0.418 in the overweight or obesity group, and 0.029, 0.428 and 0.543 in the controls (Chi-square = 5.74, P= 0.057). However, the frequency of AA+ AT genotype in case group (0.582, 82/141) was higher than that in the controls (0.457, 63/138)(Chi-square = 4.368, P= 0.037). The A allele frequency in the case group (0.326) was higher than that in the controls (0.243) (Chi-square = 4.772, P= 0.029). In both groups, the plasma glucose levels of individuals with AA+ AT genotype (4.88± 0.51 mol/L) was higher than those with TT genotypes (4.68± 0.56 mol/L)(P= 0.026). Logistic regression analysis showed that the A allele of the FTO gene was an independent risk factor for overweight or obesity (OR= 0.527; 95%CI: 0.319-0.869).

CONCLUSIONThe A allele of the fat mass and obesity associated gene might be a risk factor of overweight or obesity in Hazakh children in Xinjiang.

Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Analysis of Variance ; Case-Control Studies ; Child ; China ; ethnology ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Obesity ; blood ; genetics ; metabolism ; physiopathology ; Phenotype ; Polymorphism, Genetic ; genetics ; Proteins ; genetics

OBJECTIVEObesity is becoming a worldwide health problem. The genome wide association (GWA) study particularly for body mass index (BMI) has not been successfully conducted in the Chinese. In order to identify novel genes for BMI variation in the Chinese, an initial GWA study and a follow up replication study were performed.

METHODSAffymetrix 500K SNPs were genotyped for initial GWA of 597 Northern Chinese. After quality control, 281,533 SNPs were included in the association analysis. Three SNPs were genotyped in a Southern Chinese replication sample containing 2 955 Chinese Han subjects. Association analyses were performed by Plink software.

RESULTSEight SNPs were significantly associated with BMI variation after false discovery rate (FDR) correction (P=5.45×10⁻⁷-7.26×10⁻⁶, FDR q=0.033-0.048). Two adjacent SNPs (rs4432245 & rs711906) in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene were significantly associated with BMI (P=6.38×10⁻⁶ & 4.39×10⁻⁶, FDR q=0.048). In the follow-up replication study, we confirmed the associations between BMI and rs4432245, rs711906 in the EIF2AKE gene (P=0.03 & 0.01, respectively).

CONCLUSIONOur study suggests novel mechanisms for BMI, where EIF2AK4 has exerted a profound effect on the synthesis and storage of triglycerides and may impact on overall energy homeostasis associated with obesity. The minor allele frequencies for the two SNPs in the EIF2AK4 gene have marked ethnic differences between Caucasians and the Chinese. The association of the EIF2AK4 gene with BMI is suggested to be 'ethnic specific' in the Chinese.

Aged ; Asian Continental Ancestry Group ; genetics ; Body Mass Index ; China ; epidemiology ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Obesity ; ethnology ; genetics ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases ; genetics

OBJECTIVETo investigate the relationship between the G1057D variants of insulin receptor substrate-2(IRS2) gene and type 2 diabetes mellitus (T2DM) in subjects.

METHODSFour hundred and thirty-nine Chinese Han subjects, including 218 patients with T2DM and 221 normal controls, were selected from the Hans in the Liaoning area, and each group was divided into two subgroups according to body mass index. The G1057D variants of IRS2 were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and their relationships with T2DM were analyzed.

RESULTS(1) The frequency of G1057D variant was 29% in all subjects. The frequency of DD genotype was significantly lower in non-obese DM group than in non-obese control group. The Logistic regression analysis showed that the odds ratio of DD genotype was 0.265. The frequency of DD genotype was significantly higher in obese DM group than in obese control group. The Logistic regression analysis showed that the odds ratio of DD genotype was 3.991. (2) In the non-obese control group, the FPG and 2hCP of DD genotypes were lower than those of GG genotypes (P< 0.05, P< 0.01), the HOMA-B of DD genotypes was higher than that of GG genotype (P< 0.01). In the non-obese DM group, the waistline/hip ratio (WHR) of DD genotypes was higher than that of GG genotypes(P< 0.01). In the obese DM group, the WHR, HOMA-IR, 2hPG, 2hINS and 2hCP levels of DD genotypes were higher than those of GG genotypes, while the level of HOMA-B of DD genotypes was lower than that of GG genotypes. In the obese control group, the WHR, HOMA-IR, 2hPG, 2hINS and 2hCP levels of DD genotype were higher than those of GG genotype, and the HOMA-B level of DD genotype was lower than that of GG genotypes (P< 0.05).

CONCLUSIONThe relationships between G1057D variants of IRS2 and T2DM are mediated by obesity.

Asian Continental Ancestry Group ; genetics ; China ; Diabetes Mellitus, Type 2 ; ethnology ; etiology ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Insulin Receptor Substrate Proteins ; genetics ; Obesity ; complications ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

OBJECTIVETo study the genetic determination of fast plasma glucose (FPG) and correlation with its potential correlated traits, anthropometric measures and blood pressure.

METHODSTwo hundred and eighteen Type 2 diabetes mellitus (T2DM) pedigrees composed of 1383 Chinese Han individuals residing in the East and South-East China were analyzed. Univariate variance decomposition analyses were used to estimate the narrow-sense heritability (h(2)) of FPG, anthropometric indices and blood pressure, and bivariate quantitative genetic analyses were used to estimate the genetic and environmental correlations between FPG and anthropometric measures or blood pressure.

RESULTSWe found that FPG, blood pressure and all anthropometric indices except for waist to hip ratio were under significant genetic determination, and the h(2) was from 0.28 to 0.43. We did not find significant genetic and environmental correlation between FPG and anthropometric indices and blood pressure.

CONCLUSIONThe present study demonstrated that T2DM, obesity and hypertension were controlled by some genetic factors, and FPG shares little common genetic and environmental factors with obesity-related anthropometric indices and blood pressure in our Chinese sample population.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anthropometry ; Asian Continental Ancestry Group ; genetics ; Blood Glucose ; genetics ; Blood Pressure ; genetics ; Cardiovascular Diseases ; epidemiology ; genetics ; China ; ethnology ; Diabetes Mellitus, Type 2 ; genetics ; Fasting ; blood ; metabolism ; Female ; Genetic Predisposition to Disease ; Glucose ; genetics ; Humans ; Hypertension ; genetics ; Male ; Middle Aged ; Obesity ; genetics ; Risk Factors ; Waist-Hip Ratio ; Young Adult