OBJECTIVETo explore the association between plasma fat and glucose, cortisol and adrenocorticotropic hormone (ACTH) levels and genotypes of GR and ACTHR genes in healthy Chinese Han subjects.

METHODSTwo hundred healthy subjects were analyzed for GR and ACTHR gene polymorphisms using PCR-restriction fragment length polymorphism method. Plasma lipid, glucose, cortisol, ACTH levels were determined and correlated with the genotypes.

RESULTSNo significant difference was found between plasma lipid and glucose levels and various GR and ACTHR genotypes. Subjects with AG genotype of GR 5556A/G polymorphism had lower plasma cortisol levels than AA genotype. Compared with subjects with GG genotype of GR 4534-4536GAG/AAA [GAGAGG (GluArg)>GAAAAG(GluLys)] polymorphism, those with AG genotype had significantly lower plasma cortisol levels. Subjects with CC and CG genotypes of GR 6294C/G polymorphism also had significantly lower plasma cortisol levels compared with those with GG genotype. With regard to plasma ACTH levels, those with TT genotype of ACTHR 2T/C polymorphism were significantly lower than CC and CT genotypes, and those with AG genotype for GR 5556 A/G polymorphism were also significantly lower than AA genotype.

CONCLUSIONThere was no difference in plasma cortisol and glucose levels between subjects with GR and ACTHR gene variants. GR gene variants (5556A/G, 4534-4536GAG/AAA and 6294C/G polymorphisms) may influence plasma cortisol level, and ACTHR 2T/C, GR 5556A/G polymorphisms may decrease plasma ACTH level.

Adrenocorticotropic Hormone ; blood ; genetics ; Adult ; Blood Glucose ; genetics ; metabolism ; Female ; Genotype ; Humans ; Hydrocortisone ; blood ; genetics ; Lipids ; blood ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Glucocorticoid ; genetics

This study is to investigate the effect of diet and gene on blood-fat trait of the individual mouse. One hundred and twenty mice were fed with high fat emulsion for 4 weeks. Then the genotypes of Glut-4 were analyzed by PCR-SSCP to investigate the effect on blood-fat traits and some organ performance of mice. After fed with high fat emulsion for 4 weeks, 98 mice suffered from hyperlipidemia, while 22 mice did not. And a T/A mutation was found in 188 targeted fragments we amplified at 8,521 site, and association analysis showed that the mice carried BB genotype had higher TC, TG and LW/BW level than those of the mice with AA genotype (P < 0.05). Different Glut-4 genotypes show different sensitivities to high fat emulsion on mice.
Animals ; Glucose Transporter Type 4 ; genetics ; Hyperglycemia ; blood ; genetics ; Lipids ; blood ; Mice ; Mice, Obese ; genetics ; Polymorphism, Single Nucleotide

PURPOSE: Although some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes. MATERIALS AND METHODS: We included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined. RESULTS: Minor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02). CONCLUSION: These results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.
Adiponectin/genetics ; Asian Continental Ancestry Group ; Atherosclerosis/epidemiology/genetics ; Blood Glucose/metabolism ; Cadherins/*genetics ; Cholesterol/blood ; Female ; Humans ; Hypertension/epidemiology/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30^th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (－2.2 SD), weight 9.8 kg (－2.1 SD), body mass index 14.94 kg/m² (P₁₀-P₁₅)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.
Male ; Child ; Humans ; Child, Preschool ; Infant ; Diabetes Mellitus, Type 2/complications* ; Mutation, Missense ; C-Peptide/genetics* ; China ; Insulin/genetics* ; Glucose ; Blood Glucose ; GATA6 Transcription Factor/genetics*

BACKGROUNDEstrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha (ERalpha) gene (also named ESR1), including the XbaI and PvuII restriction enzyme polymorphisms of ESR1, which may be involved in disease pathogenesis. The aim of this study was to determine whether ERX gene polymorphisms are associated with type 2 diabetes mellitus and serum lipid level.

METHODSTwo hundred and ninety-nine patients with type 2 diabetes mellitus were compared with three hundred and forty-one health controls of Guangzhou in China, both were male and postmenopausal female residents at 51 - 70 years. ESR1 genotyping was performed using polymerase chain reaction (PCR) and PvuII and XbaI restriction fragment length polymorphism (PCR-RFLP) analysis.

RESULTSESR1 allelic frequencies of P, p and X, x alleles were 0.408, 0.592; 0.360, 0.640 in the type 2 diabetes mellitus group and 0.318, 0.682; 0.328, 0.672 in the control group, respectively. In case-control study, there was significant difference in PvuII, but not XbaI, allele frequency between the type 2 diabetes mellitus and control groups (P = 0.001 and P = 0.122). When the group was separated into men and women, the difference was significant in women (P < 0.001) but not in men (P = 0.854) with the PvuII genotype, and the effect of PvuII variant on the development of type 2 diabetes mellitus was improved with aging. In addition, PvuII genotype was associated with blood glucose [fasting blood glucose (FBG), postprandial blood glucose (PBG)] and serum lipid [total cholesterol (TC) and low density lipoprotein (LDL)-c] concentration in healthy women.

CONCLUSIONSPvuII polymorphism of ESR1 increases susceptibility to type 2 diabetes mellitus in Chinese Guangzhou women. ESR1 variants may also impact serum lipid metabolism, which might provide a mechanism connecting ESR1 to type 2 diabetes.

Aged ; Blood Glucose ; analysis ; Cholesterol, LDL ; blood ; Diabetes Mellitus, Type 2 ; blood ; genetics ; Estrogen Receptor alpha ; genetics ; Female ; Genotype ; Humans ; Lipids ; blood ; Logistic Models ; Middle Aged ; Polymorphism, Genetic

OBJECTIVETo study the distribution characteristics of adiponectin gene +45 single nucleotide polymorphisms (SNP) in Chinese children, and to determine the role of adiponectin gene +45 polymorphisms in the pathogenesis of childhood obesity.

METHODSA total of 147 Chinese obese and 118 healthy children were randomly selected and enrolled to identify adiponectin gene SNP+45 polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Plasma adiponectin levels were determined using ELISA. Waist circumference (WC), waist to hip ratio (WHR), percentage of body fat (%BF), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), serum triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), plasma fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured.

RESULTSThe allelic frequency of adiponectin gene SNP+45 in children with obesity and healthy controls were 40.5% and 25.4%, respectively. There were significant differences in the distribution of genotypes and the allelic frequency between the two groups (P<0.05). The plasma adiponectin levels were significantly higher, in contrast, %BF, HOMA-IR, TC and LDL-C levels were significantly lower in obese children with TT genotype than those in obese children with TG or GG genotype.

CONCLUSIONSThe adiponectin gene SNP+45 polymorphism may be associated with pathogenesis of obesity in children. T→G variance may be associated an increased risk of childhood obesity and result in a decreased level of adiponectin.

Adiponectin ; genetics ; Adolescent ; Blood Glucose ; analysis ; Blood Pressure ; Child ; Female ; Genotype ; Humans ; Lipids ; blood ; Male ; Obesity ; blood ; etiology ; genetics ; Polymorphism, Single Nucleotide

This study aims to explore the main mechanism of Astragali Radix-Coptis Rhizoma pair(hereinafter referred to as the pair) in the treatment of type 2 diabetes mellitus(T2 DM) based on network pharmacology and animal experiment. The main Chinese medicine compound prescriptions for T2 DM were retrieved from CNKI database and the medicinals with high frequency among these prescriptions were screened. The active components in the above medicinals were searched from TCMSP, TCMID, and previous research, targets of the components from SwissTargetPrediction and SEA, and targets for the treatment of T2 DM from DISGENET, TTD, and DrugBank. Thereby, the medicinal-component-disease-target network was constructed with Cytoscape. The targets were input in String database to yield the related proteins and the protein-protein interaction(PPI) network was constructed by Cytoscape. The biological functions of proteins in the PPI network were analyzed by Cluego. Then, high-fat high-sugar diet and 30 mg·kg~(-1) streptozotocin(STZ, intraperitoneal injection, once) were employed to induce T2 DM in rats and the T2 DM rats were classified into the control group, model group, positive drug(metformin) group, and pair group. After one month of administration, the changes of blood glucose and blood lipids [triglyceride(TG), cholesterol(CHO), low density lipoprotein(LDL), high density lipoprotein(HDL)] were detected with biochemical methods and pathological changes of islet and collagen deposition in pancreatic tissue by HE staining and Masson staining, respectively. The result showed that pair can be used for T2 DM treatment. ras-related C3 botulinum toxin substrate 1(RAC1), paraoxonase 1(PON1), beta-galactoside alpha 2,6-sialyltransferase 1(ST6 GAL1), insulin receptor(INSR), sex hormone-binding globulin(SHBG), ileal sodium/bile acid cotransporter(SLC10 A2), endothelin-1 receptor A(EDNRA), peroxisome proliferator-activated receptor A(PPARA), endothelin receptor B(EDNRB), and 5-hydroxytryptamine receptor 2 A(HTR2 A) were the targets of the pair for the treatment of T2 DM. The main biological functions of the pair were regulating the metabolism of blood glucose and li-pids and protecting the cardiovascular system. The fasting blood glucose, and serum TG, CHO, and LDL were higher(P<0.01) and the HDL was lower(P<0.05) in the model group than in the control group on the 7 th, 14 th, and 28 th days. The fas-ting blood glucose and the serum TG, CHO, and LDL decreased(P<0.05) and the serum HDL increased(P<0.05) in the metformin group and the pair group as compared with those in the model group on the 14 th and 28 th days. There were no significant differences in blood glucose, TG, CHO, LDL, and HDL between the metformin group and the pair group. Rats in the model group demonstrated damaged structures of islets and pancreas, obviously increased deposition of collagen in islets and pancreas, and blurred cell boundaries. Metformin and the pair significantly alleviated the damaged structures and collagen deposition. The pair can effectively regulate the disorders of blood glucose and lipid metabolism in T2 DM and protect the structure and functions of pancreas and islets by controlling cardiovascular system, which is worthy of clinical application and can be used for drug development.
Animals ; Blood Glucose ; Coptis ; Diabetes Mellitus, Type 2/genetics* ; Drugs, Chinese Herbal ; Metformin ; Rats ; Rhizome

OBJECTIVETo analyze the clinical characteristics of an infant with neonatal diabetes mellitus (NDM) and to sequence the ABCC8 gene of this family in order to provide a theoretical basis for the diagnosis and treatment.

METHODSThe clinical data of the patient was collected, and the proband and his direct relatives within three generations were sequenced.

RESULTSThe patient was 1-month-old, random blood glucose was more than 27.8 mmol/L, C-peptide was 33.8 pmol/L, blood gas analysis was pH 7.16, HCO3.9 mmol/L and urine alkone was 3+. Genetic testing revealed that the patient, his father, elder brother and grandmother have carried heterozygous mutation c.2690A>T(p.D897V) of the ABCC8 gene. Fluid infusion, intravenous administration of insulin and other supportive therapies were provided. After the correction of acidosis, subcutaneous insulin injection were uesd to control the blood glucose. Eight months later, blood glucose was pooly controlled. After combined with glibenclamide, blood glucose was under control.

CONCLUSIONThe patient carries a heterozygous mutation c.2690A>T(p.D897V) of ABCC8 gene, which is a novel mutation. Glibenclamide was partly effective for the patient.

Blood Glucose ; genetics ; Diabetes Mellitus ; genetics ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; genetics ; Male ; Mutation ; genetics ; Sulfonylurea Receptors ; genetics

OBJECTIVETo investigate the association of hepatitis C virus (HCV) genotype with glycolipids iron metabolism in Gansu Han population.

METHODSThe genotypes of HCV 1b type and 2a type were detected in Gansu Han HCV carriers. The Glu, Insulin, CHOL, TG, UIBC, TRF, TIBC, SF, Serum Iron, AST, ALT, TBil, IBil, DBil, ALP, GGT were measured and compared between patients with different HCV genotypes.

RESULTSThere were 84 cases with HCV1b type and 136 cases with 2a type. There were significant differences in TG, ALT, TRF, TIBC between 1b type and 2a type genotype HCV carriers.

CONCLUSIONThe 2a type HCV carriers may be more inclined to develop hyperlipidemia and liver damage, and 1b type HCV carriers are likely to have iron metabolism defect.

Adult ; Blood Glucose ; metabolism ; China ; epidemiology ; Female ; Genotype ; Hepacivirus ; genetics ; Hepatitis C ; blood ; epidemiology ; Humans ; Iron ; blood ; Lipids ; blood ; Male ; Middle Aged

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