Search

Genome-wide association studies in humans have suggested that variants of the cadherin-13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder. To examine the role of the Cdh13 and its peptide ligand adiponectin (AdipoQ) in addiction-related behaviors, we assessed Cdh13 knock-out rats and AdipoQ knock-out mice using intravenous cocaine self-administration and conditioned place preference paradigms. During intravenous cocaine self-administration, male Cdh13 heterozygous (+/−) and knock-out (−/−) rats showed increased cue-induced reinstatement compared to wild-type rats when presented with a cocaine-paired stimulus, whereas female Cdh13 rats showed no differences across genotype. Cdh13 −/− rats showed higher responding for a saccharin reinforcer and learned the choice reaction time task more slowly than wild-types. However, we found no differences between Cdh13 −/− and +/+ rats in responding for sensory reinforcement, number of premature responses in the reaction time task, tendency to approach a Pavlovian food cue, conditioned place preference and locomotor activation to cocaine (10 or 20 mg/kg). In AdipoQ −/− mice there was a significant increase in conditioned place preference to methamphetamine (1 mg/kg) but not to a range of d-amphetamine doses (0.5, 1, 2 and 4 mg/kg). Taken together, these data suggest that Cdh13 and AdipoQ regulate sensitivity to psychomotor stimulants and palatable rewards without producing major changes in other behaviors. In humans, these two genes may regulate sensitivity to natural and drug rewards, thus influencing susceptibility to the conditioned drug effects and relapse.

Aims/Introduction To investigate the association between two single nucleotide polymorphisms (SNPs; rs3774261 and rs822393) in the ADIPOQ gene and type 2 diabetes mellitus in Han Chinese from northeast China. Materials and Methods The present study comprised 993 type 2 diabetes mellitus patients and 966 unrelated controls from northeastern China. Two SNPs were sequenced using SNPscan. The distribution of genotype frequencies of the two SNPs in ADIPOQ between cases and controls, and in subgroups stratified based on body mass index, were compared using logistic regression analysis. Linear regression was used to analyze the association between each SNP and clinical indicators. Results The GG genotype of rs3774261 increased the risk of type 2 diabetes mellitus compared with the AA genotype in participants with a body mass index

Background Adiponectin (AdipoQ) is an adipose-derived plasma protein that plays an important role in hepatic lipoprotein–lipid metabolism. Emerging evidence have shown that two common polymorphisms (T45 G and G276 T) in the AdipoQ gene may contribute to increasing susceptibility to nonalcoholic fatty liver disease (NAFLD); however individually published studies show inconclusive results. This meta-analysis aimed to derive a more precise estimation of the association of AdipoQ T45 G (rs2241766 T>G) and G276 T (rs1501299 G>T) polymorphisms with NAFLD risk. Method Potential relevant studies were identified covering the following databases: PubMed, Embase, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Bio-medicine Database (CBM), and Chinese Sci-tech Journals databases. Statistical analyses were calculated using the version 12.0 STATA software (Stata Corp, College Station, TX, USA). Odds ratios (ORs) and its corresponding 95% confidence interval (CI) were calculated. Result Ten case–control studies were included with a total of 2,672 subjects, of these 1,117 being NAFLD patients and 1,555 being healthy controls. Our meta-analysis results revealed that the T variant of AdipoQ rs2241766 T>G polymorphism may be associated with an increased risk of NAFLD. There was also a significant association between the G variant of AdipoQ rs1501299 G>T polymorphism and an increased risk of NAFLD. Country-stratified analysis indicated that a higher AdipoQ rs2241766 T>G polymorphism was closely related with an increased risk of NAFLD in Chinese and Indian populations (all Ps G polymorphism and an increased risk of NAFLD (P G and rs1501299 G>T polymorphisms may contribute to an increasing susceptibility to NAFLD. Moreover, this meta-analysis also suggests for future larger studies with stratified case–control population, and greater focus on the gene–environment interactions regarding NAFLD susceptibility for valid studies.

Background Nonalcoholic fatty liver disease (NAFLD) is a significant contributor to global hepatic disorders. ADIPOQ gene single‐nucleotide polymorphisms have been associated with NAFLD susceptibility, but with inconsistent results across the studies. This study aimed to investigate the association between ADIPOQ polymorphisms (+276G>T, rs1501299 and −11377C>G, rs266729) and the risk of NAFLD. Methods PubMed, Embase, Wanfang, Web of Science, and China National Knowledge Infrastructure databases were used to identify the relevant published literature. Statistical analyses were calculated with STATA 11.0 software and RevMan 5.2. Summary odds ratios (OR) and 95% confidence intervals (CIs) were generated to assess the strength of the associations. Results Eleven relevant articles with a total of 3,644 participants (1,847 cases/1,797 controls) were included. Our meta‐analysis results revealed that ADIPOQ gene +276G>T polymorphism was not associated with NAFLD under various genetic models (allele model: OR = 0.99, 95% CI [0.69, 1.41]; dominant model: OR = 1.06, 95% CI [0.71, 1.58]; recessive model: OR = 0.83, 95% CI [0.42, 1.65]; homozygous model: OR = 0.86, 95% CI [0.38, 1.95]; heterozygous model: OR = 1.10, 95% CI [0.80, 1.53]; respectively). Moreover, no statistical significant association was found between +276G>T and NAFLD risk in the subgroups. ADIPOQ gene −11377C>G polymorphism significantly increased the risk of NAFLD (allele model: OR = 1.49, 95% CI [1.28, 1.75]; dominant model: OR = 1.64, 95% CI [1.35, 1.99]; recessive model: OR = 1.77, 95% CI [1.16, 2.70]; homozygous model: OR = 2.13, 95% CI [1.38, 3.28]; heterozygous model: OR = 1.58, 95% CI [1.29, 1.93]; respectively). Conclusion ADIPOQ gene −11377C>G may be a risk factor for NAFLD, while there was no association between ADIPOQ gene +276G>T polymorphism and the risk of NAFLD. Further studies are needed to detect the relationship between these ADIPOQ polymorphisms and NAFLD.

In cattle, the ADIPOQ gene is located in the vicinity of the quantitative trait locus (QTL) affecting marbling, the ribeye muscle area and fat thickness on BTA1. In our study, a novel variable duplication (NW_003103812.1:g.9232067_9232133dup) in the bovine ADIPOQ promoter region was identified and genotyped in seven Chinese cattle breeds. Using a reporter assay, we demonstrated that g.9232067_9232133dup decreased the basal transcriptional activity of the ADIPOQ gene in the 3T3-L1 and C2C12 cells. Furthermore, g.9232067_9232133dup suppressed the mRNA expression of the gene in adipose and muscle tissues. An association analysis indicated that the incremental variable duplication was associated with body measurements.

Objective: The excessive consumption of confectionery might have adverse effects on human health. To screen genetic factors associated with confectionery-intake frequency, a genome-wide association study (GWAS) in Japan was conducted. Design and Methods: For the discovery phase (stage 1), we conducted a GWAS of 939 noncancer patients in a cancer hospital. Additive models were used to test associations between genotypes of approximately 500,000 single-nucleotide polymorphisms (SNPs) and the confectionery-intake score (based on intake frequency). We followed-up association signals with P 0.01 in stage 1 by genotyping the SNPs of 4,491 participants in a cross-sectional study within a cohort (replication phase [stage 2]). Results: We identified 12 SNPs in stage 1 that were potentially related to confectionery intake. In stage 2, this association was replicated for one SNP (rs822396; P = 0.049 for stage 2 and 4.2 × 10−5 for stage 1+2) in intron 1 of the ADIPOQ gene, which encodes the adipokine adiponectin. Conclusions: Given the biological plausibility and previous relevant findings, the association of an SNP in the ADIPOQ gene with a preference for confectionery is worthy of follow-up and provides a good working hypothesis for experimental testing.

Summary Our aim was to investigate whether the ADIPOQ gene polymorphisms are associated with the metabolic syndrome (MetS). Genotypes of MetS patients (n= 1049) and normal controls (n= 1092) were analysed by TaqMan® assay, and serum adiponectin concentration was measured by ELISA. The variant genotypes rs266729CG; rs1063539GC, GC/CC; rs16861205AA and rs7649121AT, AT/TT (Adjusted P= 0.037, 0.044, 0.025, 0.011, 0.019, 0.020, respectively) of the ADIPOQ gene were associated with MetS. Patients with rs266729CG, CG/GG genotypes (P= 0.034, 0.035) and rs7649121AT, AT/TT genotypes (P= 0.013, 0.022) had higher levels of serum adiponectin than those with the CC and AA genotypes respectively. Furthermore, the prevalence of haplotypes GGAAAATC and GGGTAACC was lower in cases (10.7% and 4.5%) than in controls (12.1% and 5.9%) [Adjusted ORs (95% CIs) = 0.70 (0.54–0.91), 0.65 (0.46–0.92)]. The ADIPOQ gene variants associated with the risk of MetS in this study must be validated by further functional studies to reveal any potential effects on metabolism.

BACKGROUND: Obesity is associated with circulating levels of adiponectin and leptin and endometrial cancer risk. Little is known about whether single nucleotide polymorphisms (SNPs) in the genes that encode adiponectin (ADIPOQ), leptin (LEP), adiponectin receptor 1 (ADIPOR1), adiponectin receptor 2 (ADIPOR2), and leptin receptor (LEPR) are associated with endometrial cancer. METHODS: The authors selected 87 tagging SNPs to capture common genetic variants in these 5 genes. These SNPs were evaluated in 1028 endometrial cancer cases and 1932 community controls recruited from Chinese women. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Three of the 10 SNPs evaluated in the ADIPOQ gene were significantly associated with reduced cancer risk. The OR for women homozygous for the minor allele (A/A) for rs3774262 was 0.68 (95% CI, 0.48-0.97) compared with women homozygous for the major allele (G/G). Similar results were found for SNPs rs1063539 and rs12629945 in ADIPOQ, which were in linkage disequilibrium with rs3774262. These associations became nonsignificant after Bonferroni correction was applied. Controls with the minor allele A at rs3774262 had lower weight, smaller waist and hip circumferences, and lower body mass index than controls with the major allele G (all P < .05). Women homozygous for the minor allele (T/T) of rs2071045 in the LEP gene also had significantly lower risk (OR, 0.70; 95% CI, 0.54-0.90) than women homozygous for the major allele (C/C). No other SNPs in the LEP, ADIPOR1, ADIPOR2, or LEPR genes were found to be associated with cancer risk. CONCLUSIONS: Although a chance finding cannot be ruled out, the consistency of findings for gene-endometrial cancer risk and gene-obesity measurements suggests that genetic polymorphisms in the ADIPOQ gene may play a role in endometrial cancer development. Cancer 2011. © 2011 American Cancer Society.

Eur J Clin Invest 2011; 41 (12): 1330–1338 Abstract Background We hypothesized that, besides type 2 diabetes (T2D) and body mass index (BMI), circulating adiponectin concentration would be associated with variants of the ADIPOQ gene in patients with chronic heart failure (CHF). We also assessed the influence of these confounders on the prognostic value of adiponectin. Methods Plasma adiponectin was measured at entry and after 3 months in approximately 1200 patients with CHF enrolled in the GISSI-HF trial. Four common single-nucleotide polymorphisms (SNPs) spanning the ADIPOQ gene were studied: rs17300539 (−11391GA), rs266729 (−11377CG), rs2241766 (+45TG) and rs1501299 (+276GT). Associations with clinical characteristics and mortality were evaluated in patients with or without T2D. Results Adiponectin concentrations were negatively related to BMI, higher in women and older persons, but lower in patients with diabetes. T-allele carriers for rs1501299 and A-allele carriers for rs17300539 had significantly elevated adiponectin concentrations. Irrespective of diabetes, baseline plasma adiponectin was independently associated with mortality (adjusted HR [95%CI] per 1 SD increase in adiponectin concentration = 1·24[1·12–1·37], P

Reduced circulating adiponectin levels contribute to the aetiology of insulin resistance. Adiponectin circulates in three different isoforms: high molecular weight (HMW), medium molecular weight (MMW) and low molecular weight (LMW) isoforms. The genetics of adiponectin isoforms is mostly unknown. Our aim was to investigate whether and to which extent circulating adiponectin isoforms are heritable and whether they share common genetic backgrounds with insulin resistance-related traits.In a family-based sample of 640 nondiabetic White Caucasians from Italy, serum adiponectin isoforms concentrations were measured by ELISA. Three single nucleotide polymorphisms (SNPs) in the ADIPOQ gene previously reported to affect total adiponectin levels (rs17300539, rs1501299 and rs677395) were genotyped. The heritability of adiponectin isoform levels was assessed by variance component analysis. A linear mixed effects model was used to test the association between SNPs and adiponectin isoforms. Bivariate analyses were conducted to study genetic correlations between adiponectin isoforms levels and other insulin resistance-related traits.All isoforms were highly heritable (h(2) = 0.60-0.80, P = 1.0 x 10(-13)-1.0 x 10(-23)). SNPs rs17300539, rs1501299 and rs6773957 explained a significant proportion of HMW variance (2-9%, P = 1.0 x 10(-3)-1.0 x 10(-5)). In a multiple-SNP model, only rs17300539 and rs1501299 remained associated with HMW adiponectin (P = 3.0 x 10(-4) and 2.0 x 10(-2)). Significant genetic correlations (P = 1.0 x 10(-2)-1.0 x 10(-5)) were observed between HMW adiponectin and fasting insulin, homeostasis model assessment of insulin resistance, HDL cholesterol and the metabolic syndrome score. Only rs1501299 partly accounted for these genetic correlations.Circulating levels of adiponectin isoforms are highly heritable. The genetic control of HMW adiponectin is shared in part with insulin resistance-related traits and involves, but is not limited to, the ADIPOQ locus.

Summary Objective Adiponectin is an important mediator of insulin sensitivity, encoded by the ADIPOQ gene. Here we describe two Japanese–Brazilian families with hypoadiponectinaemia due to a novel mutation in ADIPOQ. Design and patients In this study, we examined the entire translated regions of adiponectin in Japanese–Brazilians, a population with one of the highest prevalence rates of diabetes worldwide. We screened 200 patients with type 2 diabetes (DM) and 240 age-matched subjects with normal glucose tolerance. Results A novel heterozygous T deletion at position 186 in exon 2 of ADIPOQ, causing a frameshift at codon 62 and leading to a premature termination at codon 168 (p.Gly63ValfsX106), was found in two individuals with diabetes. This mutation was not found in 240 nondiabetic control subjects. In addition, we screened the mutation in an expanded set of 100 nondiabetic subjects from the general Brazilian population, but we found no mutations. In addition, six family members of the probands were identified as mutation-carriers. Individuals who were mutation-carriers had markedly low plasma adiponectin concentrations compared with those without the mutation [DM: 0·65 (0·59–1·34) µg/ml vs. 5·30 (3·10–8·55) µg/ml, P

Ethnic differences may affect the association of adiponectin (Ad) multimers with coronary artery disease (CAD). We analyzed the associations of total Ad, Ad multimers, and T45G polymorphism of ADIPOQ gene with pre-existing CAD. We carried out a cross-sectional study of 216 Afro-Caribbean type 2 diabetic (T2D) subjects. Levels of total Ad, high molecular weight (HMW), middle molecular weight (MMW), and low molecular weight (LMW) isoforms were measured. Subjects were genotyped. Of the subjects studied, 57 had pre-existing CAD, 77% of whom have had myocardial infarction. Subjects with CAD had lower Ad levels (total and multimers) and a higher frequency carried the minor allele 45G, GG/TG, (18% vs. 8%, P = 0.03) than subjects without CAD. In logistic regression analysis, the models used evaluate Ad in the context of adjustment for metabolic syndrome characteristics. The adjusted odds ratio (OR) of CAD was increased significantly (by factors of 1.05-3.27) for males, older subjects, low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TGs), and carriers of the 45 G allele. For Ad, in model 1 (including only total Ad) the adjusted OR was 2.30; P = 0.03 and, in model 2 (including the three multimers, but not total Ad), the adjusted ORs were 0.73; P = 0.52 (HMW), 2.90; P = 0.01 (MMW), and 2.08; P = 0.09 (LMW). The T45G polymorphism in the ADIPOQ gene and hypoadiponectinemia were associated with CAD in our T2D subjects of predominantly African background. This effect of Ad level was mainly related to the MMW Ad form.

Genetic variation has been implicated to play some roles in the development of diabetic nephropathy. This prospective study examined if adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SN...