Genetic variability on adiponectin gene affects myocardial infarction risk: The role of endothelial dysfunction

Hui

European Journal of Endocrinology

et al. 2014

Objective: Circulating adiponectin levels have been shown to be associated with a risk of coronary heart disease (CHD). However, its primary role in protecting against the development of CHD remains controversial due to conflicting observations in prospective studies. To gain further insight into the primary role of adiponectin, our major objective was to investigate the relationship between single nucleotide polymorphisms (SNPs) of the adiponectin gene (ADIPOQ) and incident CHD in a population-based cohort with no CHD at baseline. Design and methods: We conducted a 16-year longitudinal study in 2196 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). During 33 862 person-years of follow-up, 184 subjects developed CHD (cumulative incidence rateZ5.4 per 1000 person-years). Nine ADIPOQ SNPs with potential functional relevance or shown to be associated with adiponectin levels and/or CHD were genotyped. Results: Among the nine ADIPOQ SNPs, C276GOT (rs1501299) was independently associated with incident CHD in men but not in women, even after adjustments for traditional cardiovascular risk factors (P adjusted Z5.5!10 K3 to 0.023; hazard ratioZ1.39-1.54). Furthermore, there was a significant association of the T allele of C276GOT with a lower adiponectin level (PZ0.027; b (95% CI)ZK0.05 (K0.10, K0.01). Conclusions: This study demonstrated that C276GOT may be an independent predictor of CHD development. Our findings suggest that low adiponectin levels, as may be influenced by C276GOT, confer a higher risk of CHD, in keeping with a role of hypoadiponectinaemia in the development of CHD in the general population.

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 65%

Section: Genetic Analysismentioning

confidence: 99%

See 1 more Smart Citation

Adiponectin gene variants and the risk of coronary heart disease: a 16-year longitudinal study

Hui

European Journal of Endocrinology

et al. 2014

Eur J Clin Investigation

“…Thus, serum adiponectin levels have been found to be inversely associated with components of metabolic syndrome, such as obesity, IR and T2DM [11]. However, associations between the ADIPOQ rs2241766 polymorphism and adiponectin concentration in population studies have not always been confirmed [35][36][37]. The ADIPOQ rs2241766 polymorphism is a synonymous mutation (GGT?GGG, Gly?Gly), and the way in which this variation influences metabolic phenotypes remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Association of adiponectin (ADIPOQ) rs2241766 polymorphism and dyslipidemia in HIV/HCV‐coinfected patients

Pineda‐Tenor

Berenguer

García-Broncano

et al. 2014

“…7 However, the data about the predictive value of adiponectin in coronary artery disease (CAD) are conflicting [8][9][10][11][12] ; that is, in advanced disease states (eg, in ischemic heart failure [HF]), adiponectin flags poor prognosis independently of the underlying metabolic state. 2,4,13 Therefore, a better understanding of the mechanisms controlling adiponectin levels in different CVD states may allow its use as a clinical biomarker and may identify novel therapeutic targets in patients with advanced CVD.…”

mentioning

confidence: 99%

Reciprocal Effects of Systemic Inflammation and Brain Natriuretic Peptide on Adiponectin Biosynthesis in Adipose Tissue of Patients With Ischemic Heart Disease

Antonopoulos

Margaritis

Coutinho

et al. 2014

ATVB

Self Cite

Objective-To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease. Approach and Results-In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-α, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of Salmonella typhi vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged. Conclusions-This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels.