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      Association of Adiponectin Gene ( ADIPOQ) rs2241766 Polymorphism with Obesity in Adults: A Meta-Analysis

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      1 , 2 , 1 , 2 , 3 , 1 , 2 , *
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          Abstract

          Background

          Adiponectin plays an important role in regulating glucose levels and fatty acid oxidation. Multiple studies have assessed the association between rs2241766 polymorphism in the adiponectin (ADIPOQ) gene and obesity susceptibility. However, the results are inconsistent and inconclusive. The aim of this meta-analysis was to investigate this association in adults.

          Method

          Several electronic databases were searched for relevant literature published up to November 2013. Statistical analyses were performed using software Review Manager (Version 5.02) and STATA (Version 10.0). The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random-effects model or a fixed-effect model depending on heterogeneity among studies. Q tests and Egger’s tests were performed to assess heterogeneity and publication bias. Sensitivity analysis was conducted to confirm the reliability and stability of the meta-analysis.

          Results

          A total of 2,819 obese and 3,024 controls in 18 case-control studies were included in the meta-analysis. The results indicated that compared with TT genotype, the ADIPOQ-rs2241766 GG genotype was associated with an increased risk for obesity (OR = 1.39, 95% CI: 1.11–1.73, P for heterogeneity = 0.520, I 2  = 0%) in overall studies. Whereas, GT genotype was associated with a borderland increased risk for obesity (OR = 1.13, 95% CI: 0.94–1.36, P for heterogeneity = 0.006, I 2  = 51%). The susceptibility of obesity was increased based on genotypes of TT<GT<GG ( P for trend = 0.011). Subgroup analysis of different regions revealed that the ADIPOQ-rs2241766 GG genotype increased obesity risk in the Chinese studies (OR = 1.54, 95% CI: 1.19–2.00) but not in the non-Chinese studies (OR = 1.02, 95% CI: 0.66–1.58). Similar results were observed in allelic, recessive, and dominant genetic models. There was no significant evidence of publication bias in the overall, Chinese, and non-Chinese studies ( P = 0.426, P = 0.935, and P = 0.390, respectively).

          Conclusion

          The results of this meta-analysis suggest that the ADIPOQ-rs2241766 G/T polymorphism might be associated with obesity in Chinese studies but not in non-Chinese studies in adults. Better-designed studies that consider confounding factors and assess larger sample sizes with a focus on ADIPOQ-rs2241766G/T polymorphisms and obesity are required in the future.

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          Most cited references22

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          Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.

          Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin.
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            Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.

            Adiponectin is a novel, adipose-specific protein abundantly present in the circulation, and it has antiatherogenic properties. We analyzed the plasma adiponectin concentrations in age- and body mass index (BMI)-matched nondiabetic and type 2 diabetic subjects with and without coronary artery disease (CAD). Plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in nondiabetic subjects (6.6+/-0.4 versus 7.9+/-0.5 microg/mL in men, 7.6+/-0.7 versus 11.7+/-1.0 microg/mL in women; P<0.001). The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD (4.0+/-0.4 versus 6.6+/-0.4 microg/mL, P<0.001 in men; 6.3+/-0.8 versus 7.6+/-0. 7 microg/mL in women). In contrast, plasma levels of leptin did not differ between diabetic patients with and without CAD. The presence of microangiopathy did not affect the plasma adiponectin levels in diabetic patients. Significant, univariate, inverse correlations were observed between adiponectin levels and fasting plasma insulin (r=-0.18, P<0.01) and glucose (r=-0.26, P<0.001) levels. In multivariate analysis, plasma insulin did not independently affect the plasma adiponectin levels. BMI, serum triglyceride concentration, and the presence of diabetes or CAD remained significantly related to plasma adiponectin concentrations. Weight reduction significantly elevated plasma adiponectin levels in the diabetic subjects as well as the nondiabetic subjects. These results suggest that the decreased plasma adiponectin concentrations in diabetes may be an indicator of macroangiopathy.
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              A novel serum protein similar to C1q, produced exclusively in adipocytes.

              We describe a novel 30-kDa secretory protein, Acrp30 (adipocyte complement-related protein of 30 kDa), that is made exclusively in adipocytes and whose mRNA is induced over 100-fold during adipocyte differentiation. Acrp30 is structurally similar to complement factor C1q and to a hibernation-specific protein isolated from the plasma of Siberian chipmunks; it forms large homo-oligomers that undergo a series of post-translational modifications. Like adipsin, secretion of Acrp30 is enhanced by insulin, and Acrp30 is an abundant serum protein. Acrp30 may be a factor that participates in the delicately balanced system of energy homeostasis involving food intake and carbohydrate and lipid catabolism. Our experiments also further corroborate the existence of an insulin-regulated secretory pathway in adipocytes.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                16 April 2014
                : 9
                : 4
                : e95270
                Affiliations
                [1 ]Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China
                [2 ]Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
                [3 ]Department of Hospital Management, School of Health Administration and Education, Capital Medical University, Beijing, China
                Temple University, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JJW ZL KM LZ. Performed the experiments: JJW ZL KM. Analyzed the data: JJW ZL. Contributed reagents/materials/analysis tools: JJW ZL KM LZ. Wrote the paper: JJW LZ.

                Article
                PONE-D-13-31414
                10.1371/journal.pone.0095270
                3989273
                24740426
                460dccc3-c943-44a3-8d12-1957a0506c69
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 July 2013
                : 25 March 2014
                Page count
                Pages: 9
                Funding
                This work was financially supported by the grants from Natural Science Foundation of China (30800949), Beijing Municipal Commission of Education (SQKM201210025010), Novel Star of Science Program, Beijing, China (2009A47), Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality (PXM2011-014226-07-000028), Beijing Municipal Commission of Education for Overseas Students (2011-No165). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Endocrine System
                Biochemistry
                Hormones
                Evolutionary Biology
                Population Genetics
                Genetic Polymorphism
                Genetics
                Human Genetics
                Genetic Association Studies
                Mutation
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Endocrine Physiology
                Population Biology
                Medicine and Health Sciences
                Endocrinology
                Epidemiology
                Genetic Epidemiology
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Research and Analysis Methods
                Research Design
                Clinical Research Design

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