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Background In this study, we aimed to examine the association of adiponectin (ADIPOQ) rs2241766 (+45T/G) and rs266729 (−11377C/G) gene polymorphisms with serum ADIPOQ in non-alcoholic fatty liver disease (NAFLD). Methods ADIPOQ rs2241766 and rs266729gene polymorphisms were genotyped by using TaqMan 5′-nuclease assay and serum ADIPOQ level was measured in 100 NAFLD patients and 100 healthy controls. Results The study revealed an association of G- allele of ADIPOQ rs2241766 gene polymorphism with NAFLD; X2 (P-value); 3.95 (0.047). Moreover, G-allele of ADIPOQ rs266729 gene polymorphism increased significantly in the patients compared to controls, X2 (P-value): 3.9 (0.046). The study also revealed lower serum ADIPOQ levels in NAFLD patients compared to controls (P Conclusion G-alleles of rs2241766 (+45 T/G) and rs266729 (−11377C/G) gene polymorphisms of ADIPOQ gene were associated with NAFLD, but not with serum ADIPOQ levels.

Background: Adiponectin (ADIPOQ) is a hormone primarily synthesized by adipocytes and encoded by the ADIPOQ gene, which exerts anti-inflammatory, antiatheratogenic and insulin sensitizing functions. It has been shown that its plasma concentrations are decreased in individuals with metabolic syndrome (MS) and type 2 diabetes mellitus (DM2), which could be due to variations in the gene coding for this protein. The aim of this study was to detect the +45 T>G polymorphism of the ADIPOQ gene in subjects with DM2 and MS in Maracaibo municipality, Zulia state, Venezuela. Methods: A total of 90 subjects who attended the Center for Metabolic Endocrine Research "Dr. Félix Gómez" were enrolled for this study, 46 of which had MS-DM2 and 44 of which were healthy control individuals. Genomic DNA was extracted from blood samples and PCR-restriction fragment length polymorphism analysis was carried out for the promoter region of the ADIPOQ gene. Likewise, the +45 T> G polymorphism was identified and correlated with MS and DM2 in the studied population. Results: The most frequent allele in both groups was the T allele, and the predominant genotype was homozygous T/T (79%). Genotypes with heterozygous T/G and G/G homozygous polymorphism were more frequent in the control group than in the MS-DM2 group. Regarding the individuals with T/G and G/G genotypes, statistically significant lower mean values ​​were found for fasting glucose, total cholesterol, triacylglycerides, abdominal circumference, and for the medians of systolic and diastolic blood pressure. Odds ratio were calculated for the presence or absence of MS and DM2. Conclusions: The results suggested that the presence of the G allele exerts a protective effect on the carrier individuals, thus avoiding the appearance of the aforementioned metabolic alterations.

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.

Adiponectin modulates lipid and glucose metabolism in adipose tissues and is also related to bone metabolism. Polymorphisms in the ADIPOQ gene likely have an impact on growth traits in cattle. In this study, we examined the relationship between ADIPOQ polymorphisms and body measurement parameters in Chinese beef cattle. First, we sequenced ADIPOQ and 1.2 kb of DNA upstream of its promoter, and we found 14 polymorphisms. With the luciferase reporter assay, we showed that the two polymorphisms SNP PR_–135 A>G and PR_–68 G>C, which are located in the core region of promoter, influence promoter activity of ADIPOQ. Second, we identified three haplotypes involved in these two polymorphic sites: A (A–135/C–68), B (A–135/G–68), and C (G–135/G–68). Haplotypes B and C are major haplotypes in five Chinese populations of cattle (Qinchuan, Nanyang, Jiaxian, Hazakh, and Chinese Holstein). We studied the effects of these three haplotypes on body measurements, gene expression, and promoter activity, and we found that the genotypes are associated with body measurement parameters in Qinchuan cattle. Individuals with genotype BC (AG/GG) had significantly higher body height and heart girth than others, and this result may be interpreted by the following two observations. The promoter activity with haplotype B (A/G) is significantly higher than those with A (A/C) and C (G/G) in driving reporter gene transcription; the ADIPOQ mRNA level in cattle with genotype BC (AG/GG) is relatively lower than that in cattle with genotype BB (AA/GG).

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.

Adiponectin (ADIPOQ) modulates several biological processes including energy homeostasis, glucose and lipid metabolism. The bovine ADIPOQ gene was located near the QTL affecting marbling, ribeye muscle area and fat thickness on BTA1. The gene encoding peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) was located within the QTL region of the traits on BTA6. Moreover, its protein product has various biological functions such as cellular energy homeostasis, including adaptive thermogenesis, adipogenesis and gluconeogenesis. Therefore, the ADIPOQ and PPARGC1A genes are a positional and functional candidate gene for carcass traits in beef cattle. The objectives of this study were to identify polymorphisms in the bovine ADIPOQ and PPARGC1A genes, to evaluate their associations with carcass traits in Hanwoo (Korean cattle) population. We identified nine SNPs in the ADIPOQ gene. Two SNPs (DQ156119: g.1436T > C and DQ156119: g.1454A > G) in the promoter region were recognized as new SNPs identified in Hanwoo. Association analysis indicated that the g.1454A > G SNP genotype was significantly associated with effects on LMA (P = 0.004) and BF (P = 0.021). The ADIPOQ haplotype was also found to have significant effect on the LMA. In the PPARGC1A gene, we identified 11 SNPs in the two unexplored regions (intron 3 and 5). Among them, seven SNPs were located in intron 3 and four SNPs were located in intron 5. Of these 11 putative novel SNPs, two SNPs (AY839822: g.292C > T and AY839823: g.1064C > T) with minor allele frequency (MAF) > 0.20 were examined for associations with carcass traits. The association analysis revealed that both SNPs in PPARGC1A gene were significantly associated with LMA (P < 0.05). These findings suggest that the SNPs of bovine ADIPOQ and PPARGC1A genes may be a useful molecular marker for selection of carcass traits in Hanwoo.

Our study aims to characterize the functions of the ADIPOQ gene in the process of fat deposition of pigs, thereby providing a basis for the use of this gene as a molecular marker for pork quality.We used healthy Junmu1 piglets less than 7 days of age to establish an in vitro culture system for porcine preadipocytes. Chemically synthesized short hairpin RNAs (shRNA) were transfected into porcine preadipocytes to silence the expression of the ADIPOQ gene. We monitored preadipocyte differentiation and determined the levels of the adipocyte differentiation transcription factors lipoprotein lipase (LPL), peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte fatty acid binding protein (AP2) mRNAs to investigate the effects of ADIPOQ on the differentiation of porcine preadipocytes.After transfection, the mRNA and protein levels of the ADIPOQ gene were significantly decreased (P0.01), the number of lipid droplets in the adipocytes was significantly reduced, the OD values reflecting the fat content were significantly decreased (P0.01), and the levels of LPL, PPARγ and AP2 were significantly reduced (P0.01).These results suggest that interference with ADIPOQ gene expression can inhibit the differentiation of porcine preadipocytes.

Background and Aims: The aim of this study was to determine the association of single nucleotide polymorphism rs1501299 in the ADIPOQ gene with body weight, insulin resistance, serum adipokine levels and metabolic syndrome (MetS). Methods: The study involved a population of 1,007 adult obese subjects. Parameters like body weight, fat mass, waist circumferences, blood pressure, fasting blood glucose, C-reactive protein, insulin concentration, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile and adipocytokines levels (leptin, adiponectin and resistin) were all measured. The genotype of ADIPOQ gene polymorphism (rs1501299) was evaluated. Results: Insulin levels (GG: 13.6 ± 5.1 mUI/l vs. GT: 14.1 ± 5.2 mUI/l vs. TT: 16.6 ± 5.2 mUI/l; p < 0.05) and HOMA-IR (GG: 3.3 ± 1.5 units vs. GT: 4.1 ± 1.1 units vs. TT: 4.5 ± 1.3 units; p < 0.05) were higher in T-allele carriers than they were in non-T-allele carriers. Total adiponectin levels (GG: 20.2 ± 2.4 ng/dl vs. GT: 15.8 ± 3.4 ng/dl vs. TT: 13.7 ± 1.4 ng/dl; p < 0.05) were lower in T-allele carriers than they were in non-T-allele carriers. Logistic regression analysis indicated that subjects with T allele were associated with an increased risk of MetS (OR 1.15, 95% CI 1.08-1.25, p = 0.033) and an increased risk of hyperglycemia (OR 1.99, 95% CI 1.37-2.55, p = 0.028) after adjusting by age and gender. Conclusions: These data suggest an important role of this ADIPOQ variant at position +276 on insulin resistance, total adiponectin levels and MetS.

Background: ADIPOQ gene, which encode for Adiponectin (APN), is sited on chromosome 3q27 and linked to a susceptibility locus for metabolic syndrome (MetS). The ADIPOQ rs266729 G/C gene polymorphism is significantly associated with low APN levels and linked to susceptibility to develop cancer. In addition, decreased APN serum levels are linked with tumor development and progression and inversely associated with markers of inflammation. Here, we investigate the influence of APN rs266729 G/C polymorphism on adipocytokine circulating levels and their association with MetS in colorectal cancer patients (CRC). Methods: Blood samples from 105 CRC patients (50 women and 55 men) with and without MetS were genotyped for APN rs266729 G/C polymorphism by TETRA ARMS PCR. ELISA assay was used to measure plasma levels of APN and inflammatory TNF-α cytokine. Biochemical and anthropometric parameters of MetS were also analyzed. Results: We found that CRC patients (N=75) with genotype rs266729G/C or carriers of G allele were associated with a significantly increased risk of MetS development (OR =2.9) compared to those with CC genotype (N=30). Also, CG/GG genotypes were associated with significantly lower plasma APN levels and higher TNF-α levels in comparison to CC genotype (P=0.034) and APN levels were decreased in relation to BMI increases (P=0.001). Conclusions: Our findings show that APN rs266729 G/C polymorphism is associated with lower APN levels in CRC patients, indicating that decreased circulating levels of APN may be a determinant risk factor for CRC in MetS patients.

Our aim was to investigate if single nucleotide polymorphisms (SNPs) located in the 5′ regions of leptin (LEP, -2548 G > A, rs7799039), resistin (RETN, -420 C > G, rs1862513) and adiponectin (ADIPOQ, -11391 G > A, rs17300539 and -11377 C > G, rs266729) genes were related to changes in body mass index (BMI) and metabolic variables after bariatric surgery in 60 extremely obese individuals. At baseline, ADIPOQ -11391 A-allele carriers showed higher plasma adiponectin and lower total cholesterol levels when compared to G/G homozygotes. Approximately 32 months post-surgery, a mean reduction of 35% in BMI and an important improvement in metabolic profiles were observed. In addition, for the ADIPOQ -11377 polymorphism, a higher decrease in lipid profile was associated to the C/C genotype. Moreover, individuals bearing the A-C haplotype for the two ADIPOQ SNPs were more prone to show a reduction in low-density lipoprotein levels after bariatric surgery (-43.0% A-C carriers vs. -18.1% G-G carriers, p = 0.019). We did not find any association of leptin and resistin SNPs with the clinical parameters analyzed. In summary, our results indicate that the A-C haplotype is a predictor of better lipid profile post-surgery and the studied SNPs in ADIPOQ gene are associated to changes in metabolic variables in obese individuals.

Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics–based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26–0.35) increase in fasting insulin, a 0.34-SD (0.30–0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47–2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI −0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (−0.20 SD; 95% CI −0.38 to −0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75–1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: −0.03 SD; 95% CI −0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95–1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes.

Background: Adiponectin gene expression is modulated by peroxisome proliferator–activated receptor γ, which is a transcription factor activated by unsaturated fatty acids. Objective: We investigated the effect of the interaction between variants at the ADIPOQ gene locus, age, sex, body mass index (BMI), ethnicity, and the replacement of dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates on serum adiponectin concentrations. Design: The RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) study is a parallel-design, randomized controlled trial. Serum adiponectin concentrations were measured after a 4-wk high-SFA (HS) diet and a 24-wk intervention with reference (HS), high-MUFA (HM), and low-fat (LF) diets. Single nucleotide polymorphisms at the ADIPOQ locus −11391 G/A (rs17300539), −10066 G/A (rs182052), −7734 A/C (rs16861209), and +276 G/T (rs1501299) were genotyped in 448 participants. Results: In white Europeans, +276 T was associated with higher serum adiponectin concentrations (n = 340; P = 0.006) and −10066 A was associated with lower serum adiponectin concentrations (n = 360; P = 0.03), after adjustment for age, BMI, and sex. After the HM diet, −10066 G/G subjects showed a 3.8% increase (95% CI: −0.1%, 7.7%) and G/A+A/A subjects a 2.6% decrease (95% CI: −5.6%, 0.4%) in serum adiponectin (P = 0.006 for difference after adjustment for the change in BMI, age, and sex). In −10066 G/G homozygotes, serum adiponectin increased with age after the HM diet and decreased after the LF diet. Conclusion: In white −10066 G/G homozygotes, an HM diet may help to increase adiponectin concentrations with advancing age. This trial was registered at clinicaltrials.gov as ISRCTN29111298.

The genetic mechanism of the racial distribution difference of intracranial atherosclerosis (ICAS) is unclear. The single nucleotide polymorphisms (SNPs) may be associated with different genetic susceptibility to ICAS. At present, the correlation between ADIPOQ gene SNPs and the risk of ICAS remains unknown.Continuous inpatients were selected and divided into ICAS group and control group. Computed tomography angiography was performed to observe intracranial arteries. ADIPOQ SNPs were detected using the ligase detection reaction-PCR. The correlation between the identified SNPs and ICAS was determined using the binary logistic regression analysis.This study contained 602 patients in total, including 199 ICAS and 403 control cases. The binary logistic regression analysis showed that the AG/AA genotype of the rs2241767 (OR = 2.242, 95% CI: 1.037-4.878, P = 0.040) and the AG/GG genotype of the rs182052 (OR = 1.822, 95% CI: 1.111-2.987, P = 0.017) were closely related to the risk of ICAS after adjusting for conventional cardiovascular risk factors. The haploid analysis results indicated that the incidence of the A-G haplotype of the rs2241767 and rs182052 was higher in the ICAS group than in the control group (P = 0.026).The SNPs of the ADIPOQ gene are closely related to increased risk of ICAS in Chinese Han population.

We previously reported that induction of the adipocyte-specific gene adiponectin (Adipoq) during 3T3-L1 adipocyte differentiation is closely associated with epigenetic memory histone H3 acetylation on the transcribed region of the gene. We used 3T3-L1 adipocytes and Brd4 heterozygous mice to investigate whether the induction of Adipoq during adipocyte differentiation is regulated by histone acetylation and the binding protein bromodomain containing 4 (BRD4) on the transcribed region. Depletion of BRD4 by shRNA and inhibition by (+)-JQ1, an inhibitor of BET family proteins including BRD4, reduced Adipoq expression and lipid droplet accumulation in 3T3-L1 adipocytes. Additionally, the depletion and inhibition of BRD4 reduced the expression of many insulin sensitivity-related genes, including genes related to lipid droplet accumulation in adipocytes. BRD4 depletion reduced P-TEFb recruitment and histone acetylation on the transcribed region of the Adipoq gene. The expression levels of Adipoq and fatty acid synthesis-related genes and the circulating ADIPOQ protein level were lower in Brd4 heterozygous mice than in wild-type mice at 21 days after birth. These findings indicate that BRD4 regulates the Adipoq gene by recruiting P-TEFb onto acetylated histones in the transcribed region of the gene and regulates adipocyte differentiation by regulating the expression of genes related to insulin sensitivity.

Aims To clarify the associations between plasma adiponectin levels and ADIPOQ variants with type 2 diabetes incidence in a general Japanese population. Methods We conducted a case-control study nested within the Japan Public Health Center-based Prospective Study. We measured plasma adiponectin levels and genotyped +45T > G (rs2241766) and +276 G > T (rs1501299) in the ADIPOQ gene among 417 incident diabetes cases and 1197 control subjects matched by age, sex, and area. Results After potential confounding factor adjustment, the multivariable-adjusted diabetes odds ratios (ORs) were 0.59 (95% confidence interval [CI]: 0.51–0.68) and 0.68 (95% CI: 0.60–0.78) per 1 standard deviation increment in the log-transformed levels of total- and high-molecular-weight (HMW) adiponectin levels, respectively. However, the ADIPOQ variants were not significantly associated with plasma adiponectin levels (for total adiponectin, +45 P = 0.15 and +276 P = 0.08) and diabetes risk (+45 P = 0.70 and +276 P = 0.72) under the additive genetic model. Conclusions Our prospective findings suggest that both total and HMW adiponectin levels are strongly and inversely associated with diabetes risk after adjustment for potential confounding factors; however, the ADIPOQ variants +45 and +276 are not associated with adiponectin levels and diabetes risk in the general Japanese population.

To study the association of adiponectin gene G276Т (ADIPOQ) polymorphism with the development of metabolic syndrome (MS) in ethnic Kyrgyz patients.A total of 171 patients with MS (a study group) and 117 patients without MS (a comparison group) were examined. MS was defined on the basis of the modified ATP III criteria. The genotypes of the G276T polymorphism in the adiponectin gene were determined by polymerase chain reaction-restriction fragment length polymorphism analysis.Dividing the MS and control groups by gender revealed statistically significant differences in the distribution of alleles and genotypes only among the women. There was a higher frequency of GT+TT genotypes (53% vs 34%; χ2=5.942; р=0.014) and T allele (30% vs 19%; χ2=4.489; р=0.0341) in the women with MS than in those without MS. Iin the ethnic Kyrgyz women, the T allele at the G276Т polymorphic locus in the ADIPOQ gene was associated with the development of MS (odds ratio (OR)=1.82; 95% confidence interval (CI) 1.04-3.19) and type 2 diabetes mellitus (T2DM) (OR=2.63; 95% CI, 1.05-6.56 ) with the high levels of leptin (p0.05), glucose (p0.05), triglycerides (OR=3.06; 95% CI, 1.05-8.93), low-density lipoprotein cholesterol (OR=2.80; 95% CI, 1,07-7.31) and with the lower level of high-density lipoprotein cholesterol (OR=2.9; 95% CI, 1.15-7.24).The risk for MS, T2DM, hyperglycemia, and dyslipidemia is related to the carriage of the T allele of the G276Т polymorphism in the ADIPOQ gene in ethnic Kyrgyz women.Цель исследования. Изучить ассоциацию полиморфного маркера G276Т гена адипонектина с развитием метаболического синдрома (МС) у пациентов киргизской национальности. Материалы и методы. Обследовали 171 пациента с МС и 117 лиц без МС (группа сравнения). МС констатировали на основании модифицированных критериев АТР III. Генотипы полиморфизма G276T гена адипонектина (ADIPOQ) определяли методом полимеразной цепной реакции с анализом полиморфизма длин рестрикционных фрагментов. Результаты. При разделении группы больных МС и контрольной группы по половому признаку статистически значимые различия по распространенности аллелей и генотипов выявлены только среди женщин. Наблюдалась более высокая распространенность генотипов GT+ТТ (53% против 34%; χ2=5,942; р=0,014) и аллеля Т (30% против 19%; χ2=4,489; р=0,0341) в подгруппе больных МС женщин по сравнению с женщинами из контрольной группы. У женщин киргизской национальности аллель Т полиморфного локуса G276Т гена ADIPOQ ассоциирован с развитием МС (отношение шансов - ОШ 1,82 при 95% доверительном интервале - ДИ от 1,04 до 3,19), сахарного диабета 2-го типа - СД-2 (ОШ 2,63 при 95% ДИ от 1,05 до 6,56), с высокими уровнями лептина (p0,05), глюкозы (р0,05), триглицеридов (ОШ 3,06 при 95% ДИ от 1,05 до 8,93), холестерина липопротеидов низкой плотности (ОШ 2,80 при 95% ДИ от 1,07 до 7,31) и сниженным уровнем холестерина липопротеидов высокой плотности (ОШ 2,9 при 95% ДИ от 1,15 до 7,24). Заключение. Риск развития МС, СД-2, гипергликемии и дислипидемии у женщин киргизской национальности связан с носительством аллеля Т полиморфного маркера G276T гена ADIPOQ.

Background Coronary Heart Disease (CHD) is one of the leading causes of death in the world with a projected global 82 million DALYs by 2020. Genetic and environmental factors contribute to CHD development. Here, the authors investigate the association between CHD risk and three Single Nucleotide Polymorphisms (SNPs) in the AdipoQ gene (rs3774261, rs1063537 and rs2082940); and the interaction of this association with environmental factors, in Northeast Han Chinese population. Methods Using a case–control study design, 1514 participants (754 cases and 760 controls) were investigated. Three variants in the AdipoQ gene (rs3774261, rs1063537 and rs2082940) were selected and genotyped. The online SNPstats program and SPSS 21.0 software were used for data analyses. Results The authors found that the rs3774261G allele is associated with the risk of CHD but that the rs2082940T allele protects against CHD. No significant association was found between rs1063537 and CHD risk. The study also found significant interactions between triglyceride levels and the SNPs studied (P

Summary Adiponectin (ADIPOQ) is an abundant protein hormone which belongs to a family of so-called adipokines. It is expressed mostly by adipocytes and is an important regulator of lipid and glucose metabolism. It was shown that decreased serum adiponectin concentration indicated insulin resistance and type 2 diabetes (T2DM) with the risk of cardiovascular complications. The fact that adiponectin is an insulin-sensitizing hormone with anti-diabetic, anti-inflammatory and anti-atherogenic properties, we proposed to study the association of ADIPOQ gene polymorphisms in subjects with T2DM. DNA was isolated from venous blood samples, quantified and subjected to Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR–RFLP) using suitable primers and restriction endonucleases. Adiponectin levels were measured in serum using ELISA. The genotypic, allelic and carriage rate frequencies distribution in patients and controls were analyzed by PSAW software (ver. 17.0). Odd ratios (OR) with 95% confidence interval (CI) were determined to describe the strength of association by logistic regression model. Out of the two polymorphisms studied, +10211T/G showed significant association (P = 0.042), the ‘G’ allele association being highly significant (P = 0.022). Further analysis showed that individuals with ‘GG’ haplotype were at increased risk of T2DM up to 15.5 times [P = 0.015, OR (95% CI); 15.558 (1.690–143.174)]. The present study showed that the ‘G’ allele of ADIPOQ gene (+10211T/G) plays a prominent role with respect to T2DM susceptibility in North-Indian population.

Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders. The aim of this study was to investigate possible associations between 45T/G and 276G/T variants of the ADIPOQ gene and susceptibility to PCOS. A meta-analysis of 11 published case-control studies on the 45T/G variant of the ADIPOQ gene (involving a total of 1176 patients with PCOS and 1759 controls) and eight published case-control studies on the 276G/T variant of the ADIPOQ gene (involving a total of 895 patients with PCOS and 1024 controls) was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. The comparison of G vs. T in ADIPOQ 45T/G showed significant differential susceptibility to PCOS (OR=1.397, 95% CI 1.156-1.689). A significant association was also found between PCOS susceptibility and the comparison of G vs. T in ADIPOQ 276G/T (OR 0.812, 95% CI 0.704-0.937). However, protective effects were found in both sites under the co-dominant model for Caucasians. Further studies are warranted to assess these associations in greater detail, especially in Asian populations.

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.

Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation.

Background African Americans experience disproportionately higher prevalence of type 2 diabetes and related risk factors. Little research has been done on the association of ADIPOQ gene on type 2 diabetes, plasma adiponectin, blood glucose, HOMA-IR and body mass index (BMI) in African Americans. The objective of our research was to assess such associations with selected SNPs. The study included a sample of 3,020 men and women from the Jackson Heart Study who had ADIPOQ genotyping information. Unadjusted and adjusted regression models with covariates were used with type 2 diabetes and related phenotypes as the outcome stratified by sex. Results There was no association between selected ADIPOQ SNPs with type 2 diabetes, blood glucose, or BMI in men or women. There was a significant association between variant rs16861205 and lower adiponectin in women with minor allele A in the fully adjusted model (β(SE) p = −.13(0.05), 0.003). There was also a significant association with variant rs7627128 and lower HOMA-IR among men with minor allele A in the fully adjusted model (β(SE) p = −0.74(0.20), 0.0002). Conclusions These findings represent new insights regarding the association of ADIPOQ gene and type 2 diabetes and related phenotypes in African American men and women.

To assess whether adiponectin gene (ADIPOQ) polymorphism is associated with intrauterine fetal growth and cord blood adiponectin, we investigated eight single-nucleotide polymorphisms (SNPs; rs182052, rs710445, rs16861205, rs12495941, rs1501299, rs3774261, rs2082940 and rs266729) in ADIPOQ and birth weight and cord blood adiponectin in 526 healthy neonates. We found that the neonates carrying the G allele of rs266729 had a significantly greater birth weight s.d. score than those homozygous for the C allele (CC: -0.06±0.75 versus CG: 0.20±0.64 versus GG: 0.07±0.78; P=1.65 × 10(-3), adjusted P=9.90 × 10(-3)). However, this difference was not significant after adjustment for cord blood adiponectin (P=0.04, adjusted P=0.26). The rs266729 SNP was strongly associated with cord blood adiponectin; neonates with rs266729 GG had the highest adiponectin (CC: 34.1±20.2 versus CG: 44.3±26.1 versus GG: 54.1±36.7 μg ml(-1), P=2.80 × 10(-9), adjusted P=1.68 × 10(-8)). This association remained after adjustment for birth weight s.d. score (P=6.63 × 10(-8), adjusted P=3.98 × 10(-7)). Our results suggest that the influence of the rs266729 SNP in ADIPOQ on birth weight may be dependent on circulating adiponectin.

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.

In order to evaluate the contribution of polymorphisms of the adiponectin gene, ADIPOQ, to the risk of colon cancer, we conducted a case-control study of 60 colon cancer patients and 60 age, gender and ethnicity-matched controls in the Saudi population. We tested the hypothesis by analyzing the genotypes for two single nucleotide polymorphisms (SNPs), rs1501299 (G276T) and rs2241766 (T45G), in the ADIPOQ gene. In addition, the study was also designed to assess whether the two SNPs contribute to circulating adiponectin levels. We observed an increased risk of colon cancer associated with the 276T allele. The odds ratio (OR) was 2.64 [95% confidence interval (CI), 0.49–14.6]. The G allele at the T45G polymorphism was associated with a lower risk of colon cancer (OR=0.41; 95% CI, 0.19–0.86). Our results suggest that the risk of developing colon cancer may be partially explained by genetic polymorphisms in the ADIPOQ gene.

Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.

The Adiponectin (ADIPOQ) gene encodes adipose tissue-secreted hormone, Adiponectin, which is secreted to the bloodstream by adipocytes. Adiponectin is a hormone with anti-inflammatory and anti-atherogenic properties and plays a significant role in insulin sensitivity and obesity. The genetic variations in ADIPOQ gene change the circulating adiponectin level and may cause insulin resistance. The aim of the present study is to evaluate the frequency of a common single nucleotide polymorphism (SNP) of ADIPOQ gene (+ 45T/G) and adiponectin receptor-2 (ADIPOR2) gene (+ 795G/A) in Iranian population and to correlate these data with other populations. A hundred healthy volunteers were enrolled to identify the genotype of ADIPOQ gene (+ 45T/G) and ADIPOR2 gene (+ 795G/A). This was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype frequencies for ADIPOQ (+ 45T/G) were 0.789 for TT, 0.164 for TG, and 0.0468 for GG. Allelic frequencies were 0.87 and 0.13 for T and G, respectively. Genotype frequencies for ADIPOR2 (+ 795G/A) were 0.09 for AA, 0.3 for AG, and 0.61 for GG; allelic frequencies were 0.24 for A and 0.76 for G. Comparisons between ADIPOQ and ADIPOR2 polymorphisms in Iranian population with those in other populations showed significant differences.

To study the role of the adiponectin (ADIPOQ) gene single-nucleotide polymorphism (SNP) in the susceptibility and prognosis for non-small cell lung cancer (NSCLC), we recruited 344 patients with NSCLC, of which 141 had undergone surgical resection and post-surgery follow up. For controls, there were 264 healthy volunteers for the control group, matched in age and sex with the NSCLC patients. Genotyping of SNPs in the ADIPOQ gene, namely, rs266729 (11365C>G); rs822395 (4034A>C); rs822396 (3964A>G); rs2241766 (+45T>G) were performed. Of all SNPs in the ADIPOQ gene, only the TT genotype and T allele frequency of the rs2241766 were more prevalent in NSCLC subjects than in controls. The TT genotype of rs2241766 was significantly associated with susceptibility to NSCLC before and after adjustment for age, sex, body mass index, and smoking status. In the survival analyses of subjects receiving surgical resection, only the SNPs of rs2241766 were significantly related to overall survival of NSCLC. Our results suggest that the SNP rs2241766 of the ADIPOQ gene may determine both susceptibility to NSCLC, and the prognosis for those who underwent surgical treatment.

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

Background: The genetic factors predisposing individuals with obesity or diabetes to pancreatic cancer have not been identified. Aims: To investigate the hypothesis that obesity- and diabetes-related genes modify the risk of pancreatic cancer. Methods: We genotyped 15 single nucleotide polymorphisms of fat mass and obesity-associated (FTO), peroxisome proliferators-activated receptor gamma (PPARγ), nuclear receptor family 5 member 2 (NR5A2), AMPK, and ADIPOQ genes in 1,070 patients with pancreatic cancer and 1,175 cancer-free controls. Information on risk factors was collected by personal interview. Adjusted ORs (AOR) and 95% CIs were calculated using unconditional logistic regression. Results: The PPARγ P12A GG genotype was inversely associated with risk of pancreatic cancer (AOR, 0.21; 95% CI, 0.07–0.62). Three NR5A2 variants that were previously identified in a genome-wide association study were significantly associated with reduced risk of pancreatic cancer, AORs ranging from 0.57 to 0.79. Two FTO gene variants and one ADIPOQ variant were differentially associated with pancreatic cancer according to levels of body mass index (BMI; Pinteraction = 0.0001, 0.0015, and 0.03). For example, the AOR (95% CI) for FTO IVS1-2777AC/AA genotype was 0.72 (0.55–0.96) and 1.54 (1.14–2.09) in participants with a BMI of less than 25 or 25 kg/m2 or more, respectively. We observed no significant association between AMPK genotype and pancreatic cancer and no genotype interactions with diabetes or smoking. Conclusion: Our findings suggest the PPARγ P12A GG genotype and NR5A2 variants may reduce the risk for pancreatic cancer. A positive association of FTO and ADIPOQ gene variants with pancreatic cancer may be limited to persons who are overweight. Impact: The discovery of genetic factors modifying the risk of pancreatic cancer may help to identify high-risk individuals for prevention efforts. Cancer Epidemiol Biomarkers Prev; 20(5); 779–92. ©2011 AACR.

Insulin resistance is associated with reduced serum adiponectin and increased albuminuria levels. Thus, one would anticipate an inverse relationship between circulating adiponectin and albuminuria. However, several studies have described a 'paradoxical' elevation of serum adiponectin in patients with elevated albuminuria. These findings may have been confounded by the presence of diseases and related treatments known to affect circulating adiponectin and albuminuria. We therefore studied the relationship between circulating adiponectin and albuminuria in the absence of such confounders.To this purpose, the relationship between adiponectin isoforms and albumin:creatinine ratio (ACR) was investigated in a family-based sample of 634 non-diabetic untreated white individuals with normal kidney function. We also investigated whether the two variables share a common genetic background and addressed the specific role of the gene encoding adiponectin on that background by genotyping several ADIPOQ single nucleotide polymorphisms (SNPs).ACR was directly associated with high molecular weight (HMW) adiponectin isoform (p = 0.024). The two variables shared some genetic correlation (ρ(g) = 0.38, p = 0.04). ADIPOQ promoter SNP rs17300539 was associated with HMW adiponectin (p = 4.8 × 10(-5)) and ACR (p =0.0027). The genetic correlation between HMW adiponectin and ACR was no longer significant when SNP rs17300539 was added to the model, thus reinforcing the role of this SNP in determining both traits.Our study shows a positive, independent correlation between HWM adiponectin and ACR. ADIPOQ variability is associated with HMW adiponectin and ACR, and explains some of the common genetic background shared by these traits, thus suggesting that ADIPOQ and HMW adiponectin modulate albuminuria levels.

The primary objective of the present work was to study specific features of adiponectin gene (ADIPOQ) expression in the subcutaneous and visceral fatty tissues along with the serum adiponectin level in children. The secondary objective was to elucidate the relationship between these variables and the basic anthropometric characteristics. The study included a total of 62 patients (31 boys and 31 girls at the age from 2.5 to 18 (median 13.6 (8.5-15.1) years] after they underwent planned surgical interventions. The expression of the adiponectin gene ADIPOQ was determined in paired samples of adipose tissue using the polymerase chain reaction in the real time; in addition, the serum adiponectin levels were measured. The expression of the adiponectin gene ADIPOQ was shown to be unrelated either to the age or to the sex of the children. Nor was there any significant difference between its expression in the subcutaneous and visceral tissues. The highest expression of mRNA encoding for adiponectin was recorded in the children at the Tanner stages 2-3 of sexual development. The ADIPOQ gene expression in the subcutaneous and visceral tissues of overweight children was 22% and 22.6% higher respectively than in the same tissues of normal weight children. Gene expression in the subcutaneous adipose tissue negatively correlated with the serum adiponectin level ( R = –0.38, p = 0.002), BMI SD (R = –0.35, p = 0.004 ), and the waist circumference (R = –0.36, p = 0.004). The results of the study suggest the necessity of further studies to clarify the pathophysiological role of adiponectin in the development of obesity and the related metabolic disturbances.

Type 2 diabetes mellitus (T2DM) is a worldwide health problem caused by resistance to insulin action. This chronic debilitating diseaseis preceded by a stage, known as prediabetes, in which a healthy lifestyle can delay the disease. The discovery of biochemical changes in prediabetes is important to identify individuals at risk of developing T2DM and in explaining disease pathogenesis. Adiponectin is secreted by fat cells and is linked with insulin resistance. Adiponectin levels are dysregulated in prediabetic subjects. This relationship had not been tested in Jordan. We recruited 130 subjects with prediabetes and 130 control subjects. We measured serum levels of adiponectin and genotyped subjects for three single nucleotide polymorphisms (SNPs) in the ADIPOQ gene, rs266729, rs1501299 and rs2241766. In multivariate analysis, we found that serum adiponectin lowers the risk of prediabetes (p = 0.002, odds ratio (OR), 0.764, 95% confidence interval (CI), 0.646&ndash, 0.905). The rs1501299 SNP of the ADIPOQ gene was associated with prediabetes in our population (p = 0.041). Specifically, in multivariate analysis, the GT genotype of rs1501299 increased the risk of prediabetes (p = 0.010, OR, 2.350, 95% CI, 1.231&ndash, 4.486) as well as the TT genotype (p = 0.006, OR, 4.774, 95% CI, 1.551&ndash, 14.693). Our findings indicate that serum adiponectin and SNPs in the ADIPOQ gene are associated with prediabetes in Jordan.

The association between adiponectin concentration and obesity have been reported and genetic variations of the ADIPOQ gene are known to influence the plasmatic concentration of adiponectin. Therefore, we investigated the effect of AIPOQ single nucleotide polymorphism (SNP) on obesity-related variables, and their modulation by dietary intakes in Korean women. The subjects con-sisted of 3,217 Korean women aged 40-59 years partic-ipating in the Korean Genome Epidemiology Study (KoGES). The general characteristics, anthropometric vari-ables, serum blood profiles were measured. Dietary in-take was analyzed using the Food Frequency Question-naire. Subjects with the T allele of AIPOQ rs182052 showed significantly higher obesity-related variables such as weight (p=0.005), BMI (p＜0.000), fat body mass (p=0.005), and waist-hip ratio (p=0.007) than those with the C allele. Moreover, the rs182052 T allele was associated with an increased risk of obesity prevalence (p=0.019). However, there were not any significant inter-actions observed between the genotype of ADIPOQ rs182052 and dietary intake on BMI and fat body mass. These findings suggest that the obesity-related variables may be more dominantly affected by the genotype of ADIPOQ rs182052 than dietary intake in middle aged Korean women.Keywords: ADIPOQ, single nucleotide polymorphism, rs182052, obesity, gene-diet interactions

Adiponectin is an adipocyte-secreted protein involved in a variety of metabolic processes, including glucose regulation and fatty acid catabolism. We conducted a genome-wide association study to investigate the genetic loci associated with plasma adiponectin in 1776 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). Our strongest signal for adiponectin mapped to the gene CDH13 (rs3865188, P ≤ 7.2 × 10−16), which encodes a receptor for high-molecular-weight forms of adiponectin. Strong association was also detected near the ADIPOQ gene (rs864265, P = 3.8 × 10−9) and at a novel signal 100 kb upstream near KNG1 (rs11924390, P = 7.6 × 10−7). All three signals were also observed in 1774 young adult CLHNS offspring and in combined analysis including all 3550 mothers and offspring samples (all P ≤ 1.6 × 10−9). An uncommon haplotype of rs11924390 and rs864265 (haplotype frequency = 0.050) was strongly associated with lower adiponectin compared with the most common C–G haplotype in both CLHNS mothers (P = 1.8 × 10−25) and offspring (P = 8.7 × 10−32). Comprehensive imputation of 2653 SNPs in a 2 Mb region using as reference combined CHB, JPT and CEU haplotypes from the 1000 Genomes Project revealed no variants that perfectly tagged this haplotype. Our findings provide the first genome-wide significant evidence of association with plasma adiponectin at the CDH13 locus and identify a novel uncommon KNG1–ADIPOQ haplotype strongly associated with adiponectin levels in Filipinos.

A large body of evidence indicates that the risk for developing chronic diabetic complications is under the control of genetic factors. Previous studies using a candidate gene approach have uncovered a number of genetic loci that may shape this risk, such as the VEGF gene for retinopathy, the ELMO1 gene for nephropathy, and the ADIPOQ gene for coronary artery disease. Recently, a new window has opened on identifying these genes through genome-wide association studies. Such systematic approach has already led to the identification of a major locus for coronary artery disease on 9p21 as well three potential genes for nephropathy on 7p, 11p, and 13q. Further insights are expected from a broader application of this strategy. It is anticipated that the identification of these genes will provide novel insights on the etiology of diabetic complications, with crucial implications for the development of new drugs to prevent the adverse effects of diabetes.

Family-based linkage analysis has been a powerful tool for identification of genes contributing to traits with monogenic patterns of inheritance. These approaches have been of limited utility in identification of genes underlying complex traits. In contrast, searches for common genetic variants associated with complex traits have been highly successful. It is now widely recognized that common variations frequently explain only part of the inter-individual variation in populations. ‘Rare’ genetic variants have been hypothesized to contribute significantly to phenotypic variation in the population. We have developed a combination of family-based linkage, whole-exome sequencing, direct sequencing and association methods to efficiently identify rare variants of large effect. Key to the successful application of the method was the recognition that only a few families in a sample contribute significantly to a linkage signal. Thus, a search for mutations can be targeted to a small number of families in a chromosome interval restricted to the linkage peak. This approach has been used to identify a rare (1.1%) G45R mutation in the gene encoding adiponectin, ADIPOQ. This variant explains a strong linkage signal (LOD > 8.0) and accounts for ∼17% of the variance in plasma adiponectin levels in a sample of 1240 Hispanic Americans and 63% of the variance in families carrying the mutation. Individuals carrying the G45R mutation have mean adiponectin levels that are 19% of non-carriers. We propose that rare variants may be a common explanation for linkage peaks observed in complex trait genetics. This approach is applicable to a wide range of family studies and has potential to be a discovery tool for identification of novel genes influencing complex traits.

Adiponectin is a highly abundant plasma protein synthesized nearly exclusively in adipose tissue from the ADIPOQ gene. It has excited intense interest because of robust correlation of its circulating levels with indices of insulin resistance (IR) and risk of type 2 diabetes, and their unusual inverse relationship with fat mass. It has been suggested that pharmacological strategies aimed at augmenting adiponectin levels or action may generate novel insulin-sensitizing drugs.Relevant publications were identified by searching PubMed, with secondary searches of their bibliographies.Rodent studies suggest that adiponectin exerts a direct insulin-sensitizing effect on the liver, consistent with a role in the pathogenesis of prevalent forms of IR and its sequelae. However, the complex higher-order structure of adiponectin and inconsistent reports regarding its putative receptors have complicated efforts to understand the mechanistic basis of this. No proof yet exists that adiponectin modulates insulin sensitivity in humans, and genetic, biochemical, and physiological evidence suggests that low adiponectin levels may be a consequence of IR with compensatory hyperinsulinemia. This suggests that there may be a bidirectional relationship between IR and hypoadiponectinemia in humans.The relationship between adiponectin and insulin action in humans is more complex than often suggested. Further investigation of the direction of causality in this relationship, allied to studies of the cellular mechanisms involved, will be central to improving understanding of the physiological role of this enigmatic protein, and to efforts to exploit it for therapeutic benefit.

We have examined the association of 14 tagging single nucleotide polymorphisms (tagSNPs) in peroxisome proliferator activated receptor-gamma transcripts 1 and 2 (PPARG1 and 2) and 5 tagSNPs in adiponectin (ADIPOQ) genes for their effect on type 2 diabetes mellitus (T2D) risk in Asian Indian Sikhs. A total of 554 T2D cases and 527 normoglycemic controls were examined for association with T2D and other subphenotypes of T2D. With the exception of a strong association of PPARG2/Pro12Ala with T2D (odds ratio, 0.13; 95% confidence interval, 0.03-0.56; P = .0007), no other tagSNP in the PPARG locus revealed any significant association with T2D in this population. Similarly, none of the tagSNPs in the ADIPOQ gene was associated with T2D susceptibility in single-site analysis. However, haplotype analysis provided strong evidence of association of these loci with T2D. Three-site haplotype analysis in the PPARG locus using the 2 marginally associated SNPs (P/rs11715073 and P/rs3892175) in combination with Pro12 Ala (P/rs1801282) revealed a strong association of 1 "risk" (CGC) (P = .003, permutation P = .015) and 1 "protective" (CAC) (P = .001, permutation P = .005) haplotype associated with T2D. However, the major effect still appears to be driven by Pro12Ala, as the association of these haplotypes did not remain significant when analyzed conditional upon Pro12Ala (P = .262). In addition, 2-site haplotype analysis in the ADIPOQ locus using only 2 marginally associated SNPs (AD/rs182052 and AD/rs7649121) revealed a significant protective association of the GA haplotype with T2D (P = .009, permutation P = .026). Multiple linear regression analysis also revealed significant association of an ADIPOQ variant (AD/rs12495941) with total body weight (P = .010), waist (P = .024), and hip (P = .021), although these associations were not significant after adjusting for multiple testing. Our new findings strongly suggest that the genetic variation in PPARG and ADIPOQ loci could contribute to the risk for the development of T2D in Indian Sikhs. Identification of causal SNPs in these important biological and positional candidate genes would help determine the true physiologic significance of these loci in T2D and obesity.

Over 35% of US adults are obese (BMI>30 kg/m2), with African Americans and Hispanics/Latinos disproportionately affected compared to non-Hispanic whites. Genome-wide association studies (GWAS) have identified obesity-related genetic variants, including the FTO locus, in whites of European descent

Aim The objective of this study is to assess the contribution of ADIPOQ variants to type 2 diabetes in Japanese Brazilians. Methods We genotyped 200 patients with diabetes mellitus (100 male and 100 female, aged 55.0 years [47.5–64.0 years]) and 200 control subjects with normal glucose tolerant (NGT) (72 male and 128 female, aged 52.0 years [43.5–64.5 years]). Results Whereas each polymorphism studied (T45G, G276T, and A349G) was not significantly associated with type 2 diabetes mellitus, the haplotype GGA was overrepresented in our diabetic population (9.3% against 3.1% in NGT individuals, P =.0003). Also, this haplotype was associated with decreased levels of adiponectin. We also identified three mutations in exon 3: I164T, R221S, and H241P, but, owing to the low frequencies of them, associations with type 2 diabetes could not be evaluated. The subjects carrying the R221S mutation had plasma adiponectin levels lower than those without the mutation (2.10 μg/ml [1.35–2.55 μg/ml] vs. 6.68 μg/ml [3.90–11.23 μg/ml], P =.015). Similarly, the I164T mutation carriers had mean plasma adiponectin levels lower than those noncarriers (3.73 μg/ml [3.10–4.35 μg/ml] vs. 6.68 μg/ml [3.90–11.23 μg/ml]), but this difference was not significant ( P =.17). Conclusions We identified in the ADIPOQ gene a risk haplotype for type 2 diabetes in the Japanese Brazilian population.

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.

Background Polycystic ovary syndrome (PCOS) is a common reproductive disorder. Obesity, which is linked with lower adiponectin levels, increases a woman's risk of developing PCOS; however, the association between adiponectin and PCOS is controversial. Adiponectin levels could be affected by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. This study aimed to test the relationship between serum adiponectin and PCOS in Jordan and the association between the rs2241766, rs1501299, and rs266729 SNPs in the ADIPOQ gene and PCOS. Methods One hundred and fifty-four women with PCOS and 149 age- and body mass index–matched normally menstruating controls were recruited. Serum adiponectin levels were measured using enzyme-linked immunosorbent assay. Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism analysis. Results Serum adiponectin levels were significantly lower (P=0.0064) in PCOS women and rs1501299 (+276 G/T) genotype distributions were significantly different (P=0.01) between them and normally menstruating women. Multivariate analysis revealed that adiponectin levels remained significantly lower in PCOS women (P=0.001; odds ratio [OR], 0.9; 95% confidence interval [CI], 0.84–0.96). The GT genotype of rs1501299 increased the risk of PCOS (P

Introduction: The adiponectin gene, ADIPOQ, encodes an adipocytokine, known as adiponectin hormone. This hormone is known to be associated with insulin sensitization, fat metabolism, immunity, and inflammatory response. Polymorphisms in ADIPOQ gene lower the adiponectin levels, increasing the risk for diabetes and cardiovascular diseases. Aims: The study aimed to calculate the prevalence rates of ADIPOQ polymorphisms in Indian population and to compare those prevalence rates with that of other populations. Subjects and Methods: Microarray-based genotypic data of 14 ADIPOQ polymorphisms from 703 individuals of Indian origin were used. Statistical Analysis Used: Frequency estimation, identity-by-descent, Hardy–Weinberg equilibrium, Chi-square test of significance were used for statistical analysis. Results: Allelic and genotypic frequencies of ADIPOQ polymorphisms, Chi-square tests of significance for allelic and genotypic frequencies across various populations. Conclusions: East Asians are very different from Indians in terms of allelic and genotypic frequencies of ADIPOQ polymorphisms. Europeans have similar genotypic and allelic patterns with Indians. Admixture Americans and Africans also showed significant differences with polymorphisms of the Indian population.

Background Obesity is considered a severe rapidly growing health problem all over the world. Adiponectin is an adipokine produced and secreted by adipose tissues and widely known as antidiabetic, anti-inflammatory, antiatherogenic, and cardioprotective factor. The adiponectin gene has various single nucleotide polymorphisms (SNPs). Objective Our aim of this study was to determine the genotype frequency of SNPs (276 G→T) in adiponectin gene and its relationship with the occurrence of obesity and to detect the association between adiponectin gene polymorphism and different degrees of obesity. Patients and methods A total of 96 volunteers were included and divided into the following: group I had 48 healthy nonobese control volunteers, and group II included 48 obese patients not having any disease. Anthropometric parameters were measured by standard procedures. Random blood sample was collected for routine and research investigations. PCR assay with restriction fragment length polymorphism was used to examine the adiponectin gene SNP276G>T polymorphism. Results Genotypes distributions of 276G>T polymorphisms were significantly different between obese and nonobese cases. T allele was significantly associated with obese individuals (P Conclusion The T allele and TT genotypes at the 276 locus of the ADIPOQ gene were associated with higher risk of obesity.

The current study examined the effect of single nucleotide (SNPs) polymorphisms in the ADIPOQ gene (I146T and G276T) on body mass index (BMI) of young adult women. The women were divided into underweight, normal, overweight and obese according to BMI. The circulating levels of adiponectin were measured using commercially available ELISA kits. Genetic polymorphisms were genotyped using the PCR-RFLP method. G276T and I164T SNPs are common in the examined population as the frequency of G allele of 276 SNP was 54.8% and for the T allele of 164 SNP it was 41.7%. Circulating adiponectin levels were related to BMI and were lowest in the obese versus overweight, normal weight and underweight groups (p

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. Adiponectin is an adipocyte-derived cytokine with anti-inflammatory, antidiabetic, and antiatherogenic properties. No study has reported on the association between adiponectin (ADIPOQ) gene and SLE. Our aim is to investigate the association between single-nucleotide polymorphisms in ADIPOQ gene and SLE. We examined 179 SLE patients and 237 age- and gender-matched controls from Sichuan province in China. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. Results show that there was no significant difference in the allele frequencies of rs1501299 (P=.311,OR=1.17, 95% CI: 0.86–1.59) and rs2241766 (P=.929,OR=0.99, 95% CI: 0.74–1.33) in ADIPOQ gene between SLE patients and controls. The same results were seen in their genotypes (P<.05). The allele frequencies of rs1501299 and rs2241766 polymorphisms of ADIPOQ may not be associated with SLE risk.

The adiponectin (adiponectin, C1Q and collagen domain containing) encoded by ADIPOQ is an adipokine that modulates several biological processes such as lipogenesis, gluconeogenesis, fatty acid oxidation, glucose uptake and insulin sensitivity. An objective of this study was to identify SNPs in the ADIPOQ gene both in cosmopolitan and local pig breeds reared in Italy and in Meishan samples. Resequencing of ADIPOQ gene regions in 16 pigs of 12 breeds revealed only two SNPs ( EU489740 : g.1611G > A synonymous and EU489740 : g.1735G > A missense mutations) already reported. The g.1735G > A polymorphism was genotyped by PCR-RFLP in 510 pigs from 11 breeds reared in Italy (Italian Large White, Italian Duroc, Italian Landrace, Belgian Landrace, Hampshire, Pietrain, Calabrese, Casertana, Cinta Senese, Mora Romagnola and Nero Siciliano) and from Chinese Meishan breed. The Italian local breeds were homozygous for the g.1735G allele while the Meishan samples resulted homozygous for the g.1735A allele. The polymorphism segregates in the cosmopolitan breeds, except for Hampshire, and the rarer g.1735A allele showed the highest frequency in Italian Duroc (0.12). Association analysis of g.1735G > A polymorphism with estimated breeding values (EBVs) for average daily gain (ADG), feed:gain ratio (FGR), weight of neck and loin (lean cuts, LC), weight of ham (H) and backfat thickness (BFT) were performed in Italian Duroc heavy pigs. The GA vs GG pigs showed higher least square means for ADG ( P = 0.003) and LC ( P = 0.036) EBVs and lower value for FGR EBV ( P = 0.033).