Humans ; Rural Population ; Hyperglycemia/genetics* ; Receptors, Calcitriol/genetics*

The use of atypical antipsychotics is limited by occurrence of adverse reactions such as weight gain, despite of their benefits. This article provides a comprehensive review and discussion of the most significant findings regarding obesity-related pathways and integrates these with the known mechanism of atypical antipsychotic action. The focus of this article is primarily on the genetics of obesity related pathways that may be disrupted by atypical antipsychotics. This review also discussed weight gain, hyperglycemia or occurrence of diabetes while being treated with atypical antipsychotics from the point of view of pharmacogenetics. Pharmacogenetic research seeks to uncover genetic factors that will help clinicians identify the best treatment strategies for their patients. It will aid clinically in the prediction of response and side effects, such as antipsychotic-induced weight gain, and minimize the current "trial and error" approach to prescribing in the near future. This article also presents the genetics of both central and peripheral pathways putatively involved in antipsychotic-induced weight gain while providing a comprehensive review of the obesity literature. This article also review obesity related candidate molecules which may be disrupted during atypical antipsychotic drug treatment.
Antipsychotic Agents ; Genetics ; Humans ; Hyperglycemia ; Obesity ; Pharmacogenetics* ; Weight Gain*

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

Objective To verify the expressions of genes associated with colorectal cancer with hyperglycemia and evaluate their diagnostic values.Methods Tumor tissues,distal normal intestinal mucosa,and peripheral blood samples were harvested from 109 colorectal cancer patients and peripheral blood samples from 30 diabetes patients and 30 healthy volunteers. The mRNA expressions of glucose regulated protein 78 (GRP78),NADPH oxidase-1 (NOX1),carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5),heat shock protein 60 (HSP60),and histone deacetylase 1(HDAC1) were detected by real-time quantitative polymerase chain reaction. The correlation between the gene expressions and clinicopathological parameters in colorectal cancer patients were analyzed using Pearson's correlation analysis. Diagnostic test accuracy evaluation was used to calculate the sensitivity,specificity,accuracy,predictability,Youden index,and likelihood ratio of serum gene expressions in colorectal cancer patients,and the receiver operating characteristic (ROC) curves were drawn. The area under the ROC curve was calculated to evaluate the diagnostic efficiency of the combined detection of multiple genes.Results The mRNA levels of GRP78 (P=0.001),NOX1 (P=0.022),CEACAM5 (P=0.000),HSP60 (P=0.044),and HDAC1 (P=0.047) were positively correlated with the fasting blood glucose level. The mRNA expressions of NOX1 (P=0.000,P=0.008) and HDAC1 (P=0.000,P=0.037) in tissues and serum were significantly higher in colorectal cancer patients than in patients with normal blood glucose levels. The NOX1 mRNA expression was positively correlated with the diameter of colorectal cancer (P=0.013),and the HDAC1 mRNA expression was significantly correlated with the tumor site (P=0.049),depth of primary tumor invasion (P=0.025),and TNM stage (P=0.042). The areas under the ROC curves of NOX1,CEACAM5,and HDAC1 were 0.931,0.852,and 0.860 respectively (all P=0.000). The specificity,accuracy,and negative predictive value of NOX1,HDAC1 mRNA expression in colorectal cancer patients with hyperglycemia were all above 90%. The diagnostic sensitivity and specificity of the combined detection of NOX1,CEACAM5,and HDAC1 were 98.82% and 99.93%,respectively.Conclusion Combined detection of genes associated with colorectal cancer accompanied by hyperglycemia can improve the diagnostic efficiency of early screening.
Biomarkers, Tumor ; genetics ; Carcinoembryonic Antigen ; genetics ; Case-Control Studies ; Colorectal Neoplasms ; complications ; diagnosis ; genetics ; Diabetes Mellitus ; genetics ; GPI-Linked Proteins ; genetics ; Heat-Shock Proteins ; genetics ; Histone Deacetylase 1 ; genetics ; Humans ; Hyperglycemia ; complications ; diagnosis ; genetics ; NADPH Oxidase 1 ; genetics ; ROC Curve

OBJECTIVETo determine the relationships of Met416Val and XbaI polymorphism of muscle glycogen synthase (GYS1) gene and Trg64Arg variant of the beta(3)-adrenergic-receptor (beta(3)-AR) gene with type 2 diabetes mellitus (DM) and its intermediate phenotypes in the Chinese population.

METHODSPolymerase chain reaction-oligonucleotide ligation assay and restriction fragment length polymorphism assay were used to evaluate the GYS1 and beta(3)-AR gene polymorphisms in 102 pairs of case-control Chinese spouses.

RESULTSSubjects with Met416Val variant had a significantly higher 2-hour post-glucose level than subjects without this variant had in diabetic group (P = 0.032). The Met416Val polymorphism of GYS1 gene was not significantly associated with the risk of type 2 DM (adjusted OR = 1.67; 95% CI: 0.73 - 3.81, P = 0.223). Subjects with Trp64Arg variant had a significantly higher serum uric acid level than subjects without this variant had in diabetic group (P = 0.034). The combination of BMI and Arg64 allele carrier of the beta(3)-AR gene increased the diabetic risk over four-fold (adjusted OR = 4.00; 95% CI: 1.53 - 10.45, P = 0.005).

CONCLUSIONSIn the Chinese population, Met416Val polymorphism is identified in a subgroup of diabetic subjects with high 2-hour post-glucose. It will explain why some diabetic patients appear to be genetically predisposed to developing high postpradial glucose level. The presence of the Arg64 allele in the beta(3)-AR gene may predispose patients to higher serum uric acid level.

Adult ; Aged ; Alleles ; Body Mass Index ; Diabetes Mellitus, Type 2 ; blood ; genetics ; Glycogen Synthase ; genetics ; Humans ; Hyperglycemia ; genetics ; Middle Aged ; Polymorphism, Genetic ; Postprandial Period ; physiology ; Receptors, Adrenergic, beta-3 ; genetics ; Uric Acid ; blood

OBJECTIVETo identify the relationship between genetic polymorphisms of peroxisome proliferator-activated receptor alpha (PPARalpha) intron 1A/C and metabolic syndrome (MS) in a Chinese population.

METHODSA population-based case-control study was conducted in Suzhou city, Changshu County and Ganyu County in Jiangsu Province China, on the basis of an ongoing cohort study and 2348 cases were investigated. After the exclusion of the known MS cases, 1847 eligible subjects were successfully followed-up and their waist circumference (WC), body mass index, blood pressure, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fasting plasma glucose were measured. Newly diagnosed MS patients were recruited as cases, controls were individual matched with each case. TaqMan fluorescence probe method was used to detect the genetic polymorphism of PPARalpha intron 1A/C.

RESULTSThe current analysis consisted of 389 MS patients and 389 matched controls. The C allele gene frequency of PPARalpha intron 1A/C in the case group was 22.24% (173/778), lower than that in the control group, which was 24.68% (192/778); whereas the difference was not statistically significant (chi(2) = 1.29, P > 0.05). In the genotypes AA + AC and CC, MS patients were accounted for 50.70% (363/716) and 41.94% (26/62) and hyperglycemia accounted for 21.37% (153/716) and 11.29% (7/62). Compared to the genotypes AA + AC, genotype CC was observed to be inversely associated with hyperglycemia (the adjusted OR = 0.39; 95%CI: 0.17 - 0.90) but not related to the occurrence of MS (OR = 0.75; 95%CI: 0.44 - 1.28) and other components of MS e.g., abdominal obesity (the adjusted OR = 0.67; 95%CI: 0.38 - 1.17), hypertriglyceridemia (the adjusted OR = 0.97; 95%CI: 0.53 - 1.76), low HDL-C (the adjusted OR = 0.72; 95%CI: 0.41 - 1.25) and hypertension (the adjusted OR = 0.72; 95%CI: 0.42 - 1.25) all P values > 0.05.

CONCLUSIONC allele of PPARalpha intron 1A/C is not found to be associated with MS in the Chinese population. But comparing with the genotypes AA + AC, there is an inverse association between CC genotype and hyperglycemia.

Adult ; Aged ; Alleles ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Cohort Studies ; Female ; Gene Frequency ; Genotype ; Humans ; Hyperglycemia ; etiology ; genetics ; Introns ; Male ; Metabolic Syndrome ; etiology ; genetics ; Middle Aged ; PPAR alpha ; genetics ; Polymorphism, Genetic

Apoptosis ; Cell Proliferation ; Cells, Cultured ; Gene Silencing ; Glucose ; Human Umbilical Vein Endothelial Cells ; Humans ; Hyperglycemia ; Oxidative Stress ; RNA, Long Noncoding/genetics* ; RNA, Small Interfering

AIMTo investigate the alterations of taurine transport, and taurine transporter (TAUT) mRNA by hyperglycemia in cultured rat cardiomyocytes.

METHODS3H-taurine measured the amount of taurine uptake. TAUT mRNA consents were measured using quantitative RT-PCR.

RESULTSThe cellular uptake amounts of taurine in seven groups increased with incubation time, and near to be saturated after 5 min. The uptake amount of 10, 20, and 30 mmol/L glucose groups was obviously lower than that of the control group (P < 0.05 or P < 0.01). In 30 mmmol/L glucose, taurine release obviously was decreased, as compared with that of the control. Exposure of cells to 10, 20, and 30 mmmol/L glucose decreased taurine uptake in a concentration-dependent fashion. Exposure to hyperglycemia did not affect the Km of the TAUT, but the apparent Vmax were significantly decreased (P < 0.05). In 20 and 30 mmmol/L groups, TAUT mRNA contents of myocardial cells were significantly reduced, as compared with the control group (P < 0.05).

CONCLUSIONThe data suggests that there are dysfunction of taurine uptake and downregulation of TAUT gene expression by glucose in cultured rat cardiomyocytes.

Animals ; Cells, Cultured ; Glucose ; pharmacology ; Hyperglycemia ; metabolism ; Membrane Glycoproteins ; genetics ; metabolism ; Membrane Transport Proteins ; genetics ; metabolism ; Myocytes, Cardiac ; drug effects ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Taurine ; metabolism

OBJECTIVETo explore the clinical and gene mutation characteristics of a child with maturity-onset diabetes of the young 2 (MODY2).

METHODThe clinical and follow-up data of 1 patient with MODY2 were reviewed. GCK mutational analysis was performed by PCR and direct sequencing in the proband and his family members.

RESULTThe 9 years and 6 months old boy was referred to our department for short stature and mild hyperglycemia. His fasting blood glucose was elevated to 7.4-7.8 mmol/L, hemoglobin A1C 6.7%. His height was 122 cm (-2 s), weight 25 kg (-1 s), body mass index (BMI) 16.8 kg/m(2). His physical exam was unremarkable without dysmorphic features or acanthosis nigricans. The oral glucose tolerance test (OGTT) showed fasting glucose 8.17 mmol/L, insulin <2.0 mU/L, 2 h glucose 8.69 mmol/L, insulin 5.06 mU /L. The boy was treated with insulin injection for half a year. His fasting blood glucose was stable at 5.6-8.5 mmol/L, hemoglobin A1C 6.7%-6.8%. His mother's fasting blood glucose was 6.86 mmol/L, OGTT 2 h blood glucose 10.36 mmol/L, hemoglobin A1C 6.8%. GCK sequence revealed a novel GCK mutation c.34_44+15del26 in the proband and his mother, which was co-segregated with diabetes. The boy's treatment was shifted from insulin injection to diet and exercise after the diagnosis of MODY2 was confirmed. Being followed up for 2 and a half years, his fasting blood glucose was stable at 4.6-8.0 mmol/L and hemoglobin A1C 6.8%-7.1%.

CONCLUSIONThe clinical features of MODY2 are persistent and stable fasting hyperglycemia over a period of months or years and small blood glucose increment (less than 3 mmol/L) after an OGTT (2 h glucose-fasting glucose). We identified a novel c.34_44+15del26 mutation in GCK which co-segregated with diabetes phenotype in this family.

Asian Continental Ancestry Group ; genetics ; Blood Glucose ; Child ; Diabetes Mellitus, Type 2 ; diagnosis ; genetics ; Fasting ; Follow-Up Studies ; Glucokinase ; genetics ; Glucose Tolerance Test ; Glycated Hemoglobin A ; Humans ; Hyperglycemia ; Insulin ; Male ; Mutation ; Phenotype

OBJECTIVETo study the influence of Jiangzhining decoction on the genetic expression of Liver LDLR of the rats suffered from hyperlipemia.

METHODLaboratory animals were male wister rats with hyperlipemia resulting from high fat feeding. Prescription was the douche of stomach with Jiangzhining decoction (200%) with a dosage of 1.4 g.kg-1, for 15 successive days. Total RNA was extracted from the liver tissue of treated rats and LDLRmRNA was detected by Dot blot hybridization. Expression levels of LDLRmRNA was estimated by a ratio of LDLRmRNA and beta-actin mRNA.

RESULTThe difference between expression levels of LDLRmRNA for normal group and those for hyperlipemia group (100% +/- 19% vs 39% +/- 14%) was significant (P < 0.05); and the difference between decoction group (108 +/- 8%) and hyperlipimia group was also highly significant (P < 0.01).

CONCLUSIONHigh fat feeding reduces the expression of liver LDLRmRNA while the decoction can greatly increase it. The study and development of Jiangzhining are significant in preventing and curing cadiocerebral diseases.

Actins ; biosynthesis ; genetics ; Animals ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Hyperglycemia ; metabolism ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Liver ; metabolism ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Receptors, LDL ; biosynthesis ; genetics