Association of Genetic Variants in the Adiponectin Gene with Metabolic Syndrome: A Case-Control Study and a Systematic Meta-Analysis in the Chinese Population

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Abstract

Background

The prevalence of metabolic syndrome has been rising worldwide, including in China, but knowledge on specific genetic determinants of metabolic syndrome is very limited. A number of studies have reported that polymorphisms in the ADIPOQ gene are associated with metabolic syndrome in Chinese Han populations. However, data is still conflicting. The objective of this study was to examine the associations of the adiponectin genetic variants with metabolic syndrome by a case-control study and meta-analyses in Chinese.

Methods

We first investigated the association of ADIPOQ rs2241766 (+45T>G in exon 2), rs266729 (−11377C>G in promoter) and rs1501299 (+276G>T in intron 2) polymorphisms with metabolic syndrome in a Hubei Han Chinese population with 322 metabolic syndrome patients and 161 normal controls recruited from the Yichang, Hubei. Then we comprehensively reviewed the association between ADIPOQ rs2241766/rs266729/rs1501299 and metabolic syndrome in the Chinese populations via a meta-analysis. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CI).

Results

The G allele frequency of rs2241766 in metabolic syndrome patients was significantly higher than those of controls group (29.8% vs 23.3%, OR = 1.40, P = 0.033). The logistic regression analysis adjusted by gender and age showed a nominally significant association for rs2241766 GG+GT genotype ( P = 0.065, OR = 1.55) and rs1501299 GG genotype in recessive model (OR = 1.54, P = 0.066). However, no association was observed for rs266729 in our sample. We identified thirteen studies for rs2241766 (2,684 metabolic syndrome patients and 2,864 controls), three studies for rs266729, and eleven studies for rs1501299 (2,889 metabolic syndrome patients and 3,304 controls) in Chinese. Meta-analysis indicated significant associations for the rs2241766 G allele (OR = 1.14, 95%CI = 1.05–1.24, P = 0.003), rs266729 GG+GT genotypes (OR = 0.80, 95%CI = 0.68–0.92, P = 0.003) and rs1501299 GG+TG genotypes (OR = 1.42, 95%CI 1.16–1.75, P = 0.001).

Conclusions

Our results demonstrated ADIPOQ as a pleiotropic locus for metabolic syndrome and its components in the Han Chinese population.

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Most cited references 60

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Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.

Kikuko Hotta, Tohru Funahashi, Yukio Arita … (2000)

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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PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein.

N Maeda, M. Takahashi, T. Funahashi … (2001)

Insulin resistance and its dreaded consequence, type 2 diabetes, are major causes of atherosclerosis. Adiponectin is an adipose-specific plasma protein that possesses anti-atherogenic properties, such as the suppression of adhesion molecule expression in vascular endothelial cells and cytokine production from macrophages. Plasma adiponectin concentrations are decreased in obese and type 2 diabetic subjects with insulin resistance. A regimen that normalizes or increases the plasma adiponectin might prevent atherosclerosis in patients with insulin resistance. In this study, we demonstrate the inducing effects of thiazolidinediones (TZDs), which are synthetic PPARgamma ligands, on the expression and secretion of adiponectin in humans and rodents in vivo and in vitro. The administration of TZDs significantly increased the plasma adiponectin concentrations in insulin resistant humans and rodents without affecting their body weight. Adiponectin mRNA expression was normalized or increased by TZDs in the adipose tissues of obese mice. In cultured 3T3-L1 adipocytes, TZD derivatives enhanced the mRNA expression and secretion of adiponectin in a dose- and time-dependent manner. Furthermore, these effects were mediated through the activation of the promoter by the TZDs. On the other hand, TNF-alpha, which is produced more in an insulin-resistant condition, dose-dependently reduced the expression of adiponectin in adipocytes by suppressing its promoter activity. TZDs restored this inhibitory effect by TNF-alpha. TZDs might prevent atherosclerotic vascular disease in insulin-resistant patients by inducing the production of adiponectin through direct effect on its promoter and antagonizing the effect of TNF-alpha on the adiponectin promoter.

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Adiponectin and development of type 2 diabetes in the Pima Indian population.

Robert Lindsay, Tohru Funahashi, Robert Hanson … (2002)

Adiponectin is a collagen-like circulating protein secreted by adipocytes that is proposed to mediate obesity-related resistance to insulin. In a case-control series, we assessed the role of adiponectin in later development of type 2 diabetes in 70 patients who later developed type 2 diabetes and 70 controls, matched for body-mass index, age, and sex. Cases and controls were taken from the longitudinal study of health in the Pima Indian population. At baseline, the concentration of adiponectin was lower in cases than in controls (p=0.01) and individuals with high concentrations of this protein were less likely to develop type 2 diabetes than those with low concentrations (incidence rate ratio 0.63 [95% CI 0.43-0.92]; p=0.02).

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Author and article information

Contributors

Aimin Xu: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2013

Publication date (Electronic): 4 April 2013

Volume: 8

Issue: 4

Electronic Location Identifier: e58412

Affiliations

[1 ]Hubei Key Lab of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan, China

[2 ]Wuhan Center of Medical Therapeutics, Wuhan, China

[3 ]Department of Pharmacology and Pharmacy, the University of Hong Kong, Hong Kong, China

University of Hong Kong, China

Author notes

* E-mail: huangqy@ 123456mail.ccnu.edu.cn

Competing Interests: QYH is an academic editor for PLOS ONE. This does not alter the authors‚ adherence to all the PLOS ONE policies on sharing data and materials. The other authors have declared that no competing interests exist.

Conceived and designed the experiments: QYH MG. Performed the experiments: MG DD JH. Analyzed the data: MG DD JH. Contributed reagents/materials/analysis tools: MG DD JH YQ. Wrote the paper: QYH MG YW.

Article

Publisher ID: PONE-D-12-32257

DOI: 10.1371/journal.pone.0058412

PMC ID: 3617191

PubMed ID: 23593121

SO-VID: 466ad762-276c-45c2-8a10-1e57d421123e

License:

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

Date received : 18 October 2012

Date accepted : 4 February 2013

Page count

Pages: 10

Funding

This work was supported by National Basic Research Program of China (973 Program, No. 2011CB504004) and self-determined research funds of CCNU from the colleges' basic research and operation of MOE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Association of Genetic Variants in the Adiponectin Gene with Metabolic Syndrome: A Case-Control Study and a Systematic Meta-Analysis in the Chinese Population

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Abstract

Background

Methods

Results

Conclusions

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PLOS Climate

Most cited references 60

Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.

PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein.

Adiponectin and development of type 2 diabetes in the Pima Indian population.

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