Adiponectin Gene Polymorphism (rs17300539) has No Influence on the Occurrence of Metabolic Syndrome in Women with Polycystic Ovary Syndrome

Adiponectin (rs17300539) is implicated in the pathogenesis of metabolic syndrome (MS), a common comorbidity of polycystic ovarian syndrome (PCOS). The aim of this study was to analyze the association between adiponectin gene polymorphism and incidence of MS in patients with PCOS. The study included 201 women (age 18 to 35 years), among them 81 patients with PCOS without concomitant MS, 70 subjects with PCOS and concomitant, and 50 regularly menstruating controls. Adiponectin gene polymorphism (11391 G/A, rs17300539) was determined by means of a real-time PCR. The study groups did not differ significantly in terms of their age and frequencies of various genotypes of the adiponectin gene polymorphism. The largest proportion in the whole group was Caucasian women (n = 178, 88.56%), who carried the GG genotype of the polymorphism; frequencies of GA and AA genotypes in the whole study group were 10.94% (n = 22) and 0.5% (n = 1), respectively. The presence of G or A allele of the rs17300539 adiponectin gene polymorphism was not associated with a greater likelihood of PCOS with/without concomitant MS. The hereby presented findings imply that MS is a common comorbidity in women with PCOS. However, the incidence of concomitant MS does not seem to be associated with adiponectin gene polymorphism.

Adiponectin gene polymorphisms and risk of type 2 diabetes: an updated evidence for meta-analysis

Background Growing body of evidence suggest the association between SNP − 11377 C > G and SNP + 276 G > T polymorphisms of adiponectin gene with type 2 diabetes (T2D). However, these findings have not been conclusive and consistent. The present study quantitatively evaluates the data on the association between DIPOQ − 11377C/G, and + 276G/T polymorphisms and risk of T2D through a meta-analysis. Methods A systematic search was performed in the PubMed, Web of science, Scopus and Cochrane library databases to extract published studies according to the inclusion criteria. Among the 741 studies, 391 of them were screened as full text and 31 studies were finally included in the meta-analysis. Analysis of data was performed using random-effects model. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to analyze the strength of association. Subgroup and meta-regression analyses were performed to identify the potential source of heterogeneity. Results The pooled analysis showed that there was no statistically significant association between genotypes of CC (OR = 0.76, 95% CI: 0.53–1.09, P = 0.14), CG (OR = 0.93, 95% CI: 0.72–1.20, P = 0.58) and GG (OR = 1, 95% CI: 0.80–1.26, P = 0.94) ADIPO − 11377 polymorphism with increased risk of T2D. In addition, the results revealed a trend toward an increased risk of T2D for the SNP + 276 TT genotype (OR = 0.87, 95% CI: 0.77–0.98, P = 0.026) as compared with the GT and GG genotypes. Subgroup analysis by ethnicity indicated significant association between the TT genotype of the SNP + 276 and increased risk of T2D among Europeans. Met-regression demonstrated significant association between the GT genotype of + 276 polymorphism with risk of T2D in male individuals (slope: 0.0006; 95% CI: 0.0002–0.0009; P < 0.001). Conclusions Collectively, our findings demonstrated a positive association between ADIPOQ + 276 G > T polymorphism with increased risk of T2D in male individuals with European ethnicity. Graphical Abstract

Associations of the Polymorphisms in ADIPOQ with Circulating Levels of Adiponectin and Lipids: A Meta-Analysis

The relationships between the rs266729, rs1501299, and rs2241766 polymorphisms in adiponectin gene (ADIPOQ) and circulating levels of adiponectin and lipids remain to be clarified. Databases including PubMed and Embase were searched for eligible studies. The random-effects model was used, and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to estimate the differences in circulating levels of adiponectin and lipids between the subjects with different genotypes. A total of 12 810, 17 319, and 21 361 subjects were identified in the analyses for the rs266729, rs1501299, and rs2241766 polymorphisms, respectively. G allele carriers of the rs266729 polymorphism had lower levels of adiponectin (SMD=–0.28, 95% CI=–0.43 to–0.12) and high-density lipoprotein cholesterol (HDL-C) (SMD=–0.10, 95% CI=–0.17 to–0.02) than CC homozygotes; T allele carriers of the rs1501299 polymorphism had higher levels of adiponectin (SMD=0.21, 95% CI=0.05 to 0.36) and HDL-C (SMD=0.09, 95% CI=0.04 to 0.15) and lower levels of triglycerides (SMD=–0.06, 95% CI=–0.12 to–0.01) than GG homozygotes; G allele carriers of the rs2241766 polymorphism had lower levels of adiponectin (SMD=–0.18, 95% CI=–0.31 to–0.05) and HDL-C (SMD=–0.12, 95% CI=–0.20 to–0.04) than TT homozygotes. This meta-analysis suggests that the rs266729, rs1501299, and rs2241766 polymorphisms of ADIPOQ are significantly associated with circulating levels of adiponectin and lipids, which may partly explain the associations between these polymorphisms and coronary artery disease.

The association of adiponectin gene polymorphisms with susceptibility and progression of NAFLD in a cohort of Egyptian patients

Background Several genetic polymorphisms have been proven to play a key role in the progression of non-alcoholic fatty liver disease (NAFLD) from simple steatosis to NASH with fibrosis. Our aim was to study the effect of single nucleotide polymorphisms (SNPs) in the adiponectin gene, namely rs266729 and rs3774261, on susceptibility to NAFLD and disease progression. Results There was a definitive association between polymorphisms of the studied SNPs and NAFLD. Among rs266729, CG was significantly higher among patients than controls showing increased risk for NAFLD (P<0.05). AA genotype of the rs3774261 variant was significantly lower in patients than in controls (P value< 0.001) while AG and GG genotypes were significantly higher in patients than in controls (P value<0.05); A allele was significantly higher among controls (P=0.019) which might have a protective effect. None of the variants correlated significantly with the degree of steatosis. Using multivariate regression analysis, there was no significant correlation with any of the independent risk factors to the degree of steatosis. Conclusions There was an association between polymorphisms of the studied SNPs of rs266729 and rs3774261 of the adiponectin gene and NAFLD.

Adiponectin Synthesis, Secretion and Extravasation from Circulation to Interstitial Space

Adiponectin, an adipokine that circulates as multiple multimeric complexes at high levels in serum, has antidiabetic, anti-inflammatory, antiatherogenic, and cardioprotective properties. Understanding the mechanisms regulating adiponectin’s physiological effects is likely to provide critical insight into the development of adiponectin-based therapeutics to treat various metabolic-related diseases. In this review, we summarize our current understanding on adiponectin action in its various target tissues and in cellular models. We also focus on recent advances in two particular regulatory aspects; namely, the regulation of adiponectin gene expression, multimerization, and secretion, as well as extravasation of circulating adiponectin to the interstitial space and its degradation. Finally, we discuss some potential therapeutic approaches using adiponectin as a target and the current challenges facing adiponectin-based therapeutic interventions.