OBJECTIVETo understand the relationships between CDH13 (T-cadherin) genetic polymorphisms, adiponectin levels and ischemic stroke, and possible interactions between CDH13 polymorphisms and other risk factors.

METHODSWe recruited 342 Chinese ischemic stroke sib pairs. We genotyped rs4783244 and rs7193788 on CDH13 using time-of-flight mass spectrometry genotyping technology and measured total and high-molecular weight (HMW) adiponectin levels. We investigated associations between SNPs and ischemic stroke, and interactions between SNPs and other risk factors using multi-level mixed-effects regression model.

RESULTSIn individuals without ischemic stroke, CDH13 rs4783244 was associated with total adiponectin levels (per T: Coef = -0.257, P = 0.001). CDH13 rs7193788 was associated with total adiponectin levels (per A: Coef = -0.221, P = 0.001) and HMW adiponectin levels (per A: Coef = -0.163, P = 0.003). rs7193788 was significantly associated with ischemic stroke (GA/AA vs. GG: OR = 1.55, 95% CI: 1.07 to 2.24, P = 0.020) after Bonferroni correction (α = 0.025). There was an interaction between rs7193788 and diabetes (P = 0.036). Compared to diabetes-free individuals with rs7193788 GG genotype, diabetes patients with rs7193788 GA/AA genotypes had higher risks for ischemic stroke (OR = 2.64, 95% CI: 1.58-4.40, P < 0.001).

CONCLUSIONCDH13 genetic polymorphisms are associated with adiponectin levels and ischemic stroke. An interaction is found between CDH13 SNP and diabetes for ischemic stroke.

Adiponectin ; blood ; Aged ; Brain Ischemia ; blood ; genetics ; Cadherins ; genetics ; China ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Risk Factors ; Stroke ; blood ; genetics

Rats were exposed to 1 or 10 μg/mL bisphenol A (BPA) in water during pregnancy and lactation. Offspring rats were given normal water and a standard diet from weaning to postnatal day (PND) 50. Perinatal exposure to BPA resulted in significantly increased body weight, visceral adipose tissue, abnormal serum lipids, and lower adiponectin (ADP) levels in both female and male offspring rats. Liver adipose triglyceride lipase (Atgl) mRNA levels and ADP protein in visceral adipose tissue were significantly decreased in BPA-exposed offspring rats. In both female or male offspring rats, obesity and dyslipidemia induced by perinatal exposure to BPA were associated with down regulation of Atgl mRNA in liver and ADP protein in visceral adipose tissue.
Adiponectin ; metabolism ; Adipose Tissue ; metabolism ; Animals ; Benzhydryl Compounds ; adverse effects ; metabolism ; Body Weight ; Dyslipidemias ; enzymology ; etiology ; metabolism ; physiopathology ; Female ; Humans ; Lipase ; genetics ; metabolism ; Lipids ; blood ; Male ; Obesity ; enzymology ; etiology ; metabolism ; physiopathology ; Phenols ; adverse effects ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; enzymology ; etiology ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley

PURPOSE: Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). MATERIALS AND METHODS: We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. RESULTS: Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cho-lesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. CONCLUSION: Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.
Adiponectin/blood/*genetics ; Adult ; Aged ; Alleles ; Blood Pressure/genetics ; Body Mass Index ; Cadherins/blood/*genetics ; Cholesterol ; Cholesterol, LDL ; Female ; Genotype ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Insulin ; Interleukin-6 ; Leptin/genetics ; Lipoproteins, HDL/genetics ; Male ; Middle Aged ; Obesity/blood ; Polymorphism, Genetic ; Triglycerides/genetics ; Tumor Necrosis Factor-alpha/genetics ; Vascular Diseases/*drug therapy

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

OBJECTIVETo assess the association between a rs7903146(C/T) polymorphism of TCF7L2 gene and metabolic syndrome (MS), plasma lipoprotein, and plasma adiponectin (PA) in Chinese Korean and Han populations from Yanbian region.

METHODSPolymerase chain reaction and DNA sequencing were used to determine the genotype of rs7903146 in 310 Chinese Korean (190 in case group and 120 in control group) and 344 Chinese Han (255 in case group and 89 in control group). ELIAS was used to test serum insulin (INS) and PA.

RESULTSThe frequency of T allele was higher in ethnic Han compared with ethnic Koreans (0.022 vs. 0.008), lower than that of Europeans (0.279) and Africans (0.257), but similar to those of Beijing Chinese and Japanese. For ethnic Korean Chinese, the frequencies of TT and CT genotypes as well as the T allele in patients with EH were significantly higher than those of the control group (P< 0.01), which also showed an increasing trend for both MS and T2DM groups (P=0.09 and P=0.07, respectively). By contrast, for Chinese Han, the frequencies of genotypes and particular allele in patients with MS, T2DM and EH showed no significant difference from those of the control group. For T2DM, EH, and control groups, PA level of individuals with CT or TT genotypes was significantly higher compared with that of the CC genotype (P< 0.05). The TC and LDL-C levels were significantly higher in T2DM, MS and EH groups compared with those of the control group. The PA level was lower in MS group compared with the control group.

CONCLUSIONThe T allele of SNP rs7903146 of TCF7L2 gene may be a risk factor for EH in Chinese Korean population from Yanbian region. The T allele also affects the PA level; lower PA is a risk factor for MS. The rs7903146 polymorphism showed a racial and ethnic difference.

Adiponectin ; blood ; Base Sequence ; China ; ethnology ; Female ; Humans ; Male ; Metabolic Syndrome ; blood ; enzymology ; genetics ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Transcription Factor 7-Like 2 Protein ; genetics ; metabolism

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

OBJECTIVETo investigate the relationship between visceral fat depot and adiponectin level in OLETF rats.

METHODSTwenty male OLETF rats and 10 male Long-Evans Tokushima Otsuka (LETO) rats were subjected to regular oral glucose tolerance test (OGTT). The rats were sacrificed at the ages of 8, 32 and 40 weeks for measurements of the body weight, blood glucose, blood lipid level, blood insulin, and weight of the visceral fat.

RESULTSCompared with LETO rats, OLETF rats had significantly higher body weight and visceral fat with impaired glucose tolerance (P<0.05). OLETF rats also had higher blood insulin, TG, FFA and CHOL levels (P<0.05). The plasma adiponectin level was significantly lower in OLETF rats than in LETO rats at different ages (P<0.05). The adiponectin mRNA level in the adipose tissue of OLETF rats was comparable with that in LETO rats, but significantly decreased at 32 and 40 weeks of age (P<0.01).

CONCLUSIONPlasma adiponectin level is significantly correlated to insulin sensitivity and visceral fat depots in OLETF rats, but a lowered APN mRNA expression level is not the main reason for a decreased plasma adiponectin level in the early stage.

Adiponectin ; blood ; genetics ; metabolism ; Animals ; Insulin Resistance ; Intra-Abdominal Fat ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred OLETF

OBJECTIVETo study the effects of Liuweidihuang pills in preventing diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

METHODSForty male OLETF rats were randomized equally into Liuweidihuang pill group and control group, with 10 male LETO rats as the normal control group. In Liuweidihuang pill group, the rats were given the pills intragastrically at the daily dose of 2.4 mg/kg since 8 weeks of age, and the rats in the other two groups received water instead. Blood glucose of the rats was determined by oral glucose tolerance test (OGTT), and the body weight and food intake were monitored on a weekly basis. At 8, 32 and 40 weeks, the rats were sacrificed and the expression level of adiponectin mRNA in the adipose tissue was detected using RT-PCR.

RESULTSTreatment with Liuweidihuang pills significantly lowered the increment of the blood glucose and postponed the onset of hyperglycemia in the rats. Compared with the control group, the rats in Liuweidihuang pill group showed significantly increased expression of adiponectin mRNA in the adipose tissue. The rats receiving Liuweidihuang pills developed diabetes at 30 weeks of age with an incidence of 28.6% at 40 weeks, significantly lower than that in the control group (P<0.01).

CONCLUSIONLiuweidihuang pills can significantly increase the expression of adiponectin mRNA in the adipose tissue and decrease the incidence of type 2 diabetes in OLETF rats.

Adiponectin ; genetics ; metabolism ; Adipose Tissue ; metabolism ; Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Phytotherapy ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Inbred OLETF

OBJECTIVETo explore the difference of serum adiponectin (APN) level in hypertensive patients of phlegm-dampness constitution (PDC) and in those of non-PDC, as well as its association with APN gene polymorphisms.

METHODSSerum APN levels in 250 hypertensive patients (137 of PDC and 113 of non-PDC) were determined, and a correlation study was performed on 8 selected single nucleotide polymorphism (SNP) of APN gene.

RESULTSSignificant differences of serum APN levels were observed between PDC and non-PDC patients (5.07 +/- 0.35 microg/mL vs 6.41 +/- 0.39 microg/mL, P = 0.045). No significant difference in polymorphism distribution of the 8 SNP sites of APN genes was found between patients of different constitutions (P > 0.05). Serum APN level was significantly lower in PDC patients than in non-PDC patients in sites of APN gene rs1063537 (3224C/T) polymorphism TT genotype (2.580 +/- 1.029 microg/mL vs 6.011 +/- 0.945 microg/mL, P = 0.017) and CT genotype (5.113 +/- 0.968 microg/mL vs 7.812 +/- 0.161 microg/mL, P = 0.021), while that of CC genotype was insignificant between the two constitutions (5.426 +/- 0.591 microg/mL vs 6.130 +/- 0.668 microg/mL).

CONCLUSIONSerum APN level was significantly lower in hypertensive patients of PDC than in those of non-PDC. Moreover, the APN gene SNP3224 T allele carrier might be a hereditary feature of APN abnormity.

Adiponectin ; blood ; genetics ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Hypertension ; blood ; genetics ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Polymorphism, Single Nucleotide

Adiponectin stimulates cholesterol efflux in macrophages and low adiponectin may in part contribute to disturbed reverse cholesterol transport in type 2 diabetes. Monocytes express high levels of annexin A6 that could inhibit cholesterol efflux and it was investigated whether the atheroprotective effects of adiponectin are accompanied by changes in annexin A6 levels. Adiponectin reduces annexin A6 protein whereas mRNA levels are not affected. Adiponectin-mediated activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and AMP-activated protein kinase (AMPK) does not account for reduced annexin A6 expression. Further, fatty acids and lipopolysaccharide that are elevated in obesity do not influence annexin A6 protein levels. Annexin A6 in monocytes from overweight probands or type 2 diabetic patients is significantly elevated compared to monocytes of normal-weight controls. Monocytic annexin A6 positively correlates with body mass index and negatively with systemic adiponectin of the blood donors. Therefore, the current study demonstrates that adiponectin reduces annexin A6 in monocytes and thereby may enhance cholesterol efflux. In agreement with these in vitro finding an increase of monocytic annexin A6 in type 2 diabetes monocytes was observed.
AMP-Activated Protein Kinases/metabolism ; Adiponectin/*pharmacology ; Animals ; Annexin A6/genetics/*metabolism ; Body Mass Index ; CHO Cells ; Case-Control Studies ; Cell Culture Techniques ; Cholesterol/metabolism ; Cricetinae ; Cricetulus ; Diabetes Mellitus, Type 2/*blood ; Down-Regulation/*drug effects ; Electrophoresis, Polyacrylamide Gel ; Humans ; Immunoblotting ; Male ; Middle Aged ; Monocytes/*metabolism ; Obesity/*blood ; PPAR alpha/metabolism ; RNA, Messenger/metabolism ; Recombinant Proteins/pharmacology ; Reverse Transcriptase Polymerase Chain Reaction