Adiponectin G276T gene polymorphism is associated with cardiovascular disease in Japanese patients with type 2 diabetes
Introduction
Adiponectin, an adipokine secreted by differentiated adipocytes, plays pivotal roles in the regulation of insulin action and metabolisms of glucose and lipids [1], [2], [3], [4]. It also has anti-atherogenic properties via action on endothelium, inhibition of vascular smooth muscle cell proliferation, and the anti-inflammatory effects on the cellular components of the vascular wall [5], [6]. Indeed, previous studies have shown that reduced serum adiponectin levels are associated with obesity, insulin resistance, type 2 diabetes (T2DM), and cardiovascular disease (CVD) [7], [8], [9], [10], [11], [12], [13], [14], suggesting that adiponectin could be a link between obesity and atherosclerosis.
Since serum adiponectin level is affected by genetic factors such as SNPs in the adiponectin (ADIPOQ) gene as well as environmental factors including nutritional behavior and physical activity, the association between the risk of CVD and several SNPs in the adiponectin gene that potentially modulates serum adiponectin levels has been evaluated. Among these SNPs, 1 SNP located 276 bp downstream of the translational start site (ADIPOQ G276T, rs1501299) was associated with decreased serum adiponectin level, greater insulin resistance, and an increased risk of type 2 diabetes [15]. However, it is still controversial whether this polymorphism is associated with the development of CVD [16], [17], [18], [19], [20], [21], [22], [23].
In this study, we examined the relationship between ADIPOQ gene G276T polymorphism and CVD in a large cohort of Japanese type 2 diabetic patients.
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Subjects
Japanese type 2 diabetic subjects who periodically attended the outpatient clinics of diabetes in 9 participating hospitals (Osaka University Medical Hospital, Juntendo University Hospital, Ehime Prefectural Central Hospital, Ehime Prefectural Imabari Hospital, Imamura Clinic, Ishibashi Clinic, Kanda Naika Clinic, Naka Memorial Clinic, Kawai Clinic) during 1 year (January–December period in 2005) in Japan were asked to participate in this study. We considered all the non-elderly adult (20–64
ADIPOQ G276T polymorphism and CVD in T2DM subjects
Table 1 shows the general characteristics of the subjects in this study. Among a total of 2637 subjects, 213 subjects were defined as having CVD (113 subjects had myocardial infarction, 92 had cerebral infarction, and 8 had both of them). The prevalence of the G276T genotypes was as follows: GG, 51.5%; GT, 39.7%; TT, 8.8%; and the genotype distribution was in Hardy–Weinberg equilibrium.
The frequency of G allele was significantly higher in subjects with CVD as compared to those without it (77.2%
Conclusions
Firstly, we performed a simple association analysis, where the association between ADIPOQ gene G276T polymorphism and the prevalence of CVD was examined in the whole type 2 diabetic subjects with and without obesity. This analysis revealed that the G allele or GG genotype of this polymorphism could be a risk factor for CVD in Japanese type 2 diabetic patients. This finding was consistent with several previous reports in other ethnic populations with and without T2DM [16], [18], [19], [23] but
Acknowledgements
Declaration of competing interests: Nothing to declare.
Author contributions: N.K. and H.K. researched data and wrote the manuscript. T.M., M.T., M.M., I.S., K.O., T.O., K.K., F.K., K.I., researched data. A.K., R.K, M.M., T.F., Y.Y. contributed to the discussion. I.S. reviewed/edited the manuscript. All authors reviewed and approved the report.
The guarantor's name: Naoto Katakami.
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The relationship between circulating adiponectin, ADIPOQ variants and incident cardiovascular disease in type 2 diabetes: The Fremantle Diabetes Study
2018, Diabetes Research and Clinical PracticeCitation Excerpt :The ADIPOQ gene regulates serum adiponectin concentrations [9–13]. Genetic variants have been associated with CVD in people with or without diabetes in some [14–17] but not other [18–20] studies. Most relevant studies have, however, examined a limited number of variants including rs266729 (−11377C > G), rs182052 (−10066G > A), rs822395 (−4034A > C), rs822396 (−3964A > G), rs2241766 (+45 T/G) and rs1501299 (+276G > T).
Adiponectin gene variants and decreased adiponectin plasma levels are associated with the risk of myocardial infarction in young age
2018, GeneCitation Excerpt :One of the most common and widely studied variants is rs1501299:G > T (276G/T). The GG genotype was significantly associated with cardiovascular disease in European (Chiodini et al., 2010) and Japanese patients (Katakami et al., 2012). There was no such correlation in Chinese patients in one study (Liu et al., 2011), however, the T allele may be associated with the decreased risk of CAD in the Chinese Han population in another study (Zhang B.C. et al., 2012), whereas the presence of the T variant of rs1501299:G > T is independently associated with increased myocardial infarction risk in the Greek population (Antonopoulos et al., 2013).
The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases
2015, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :Secreted by adipose cells, adiponectin increases insulin sensitivity, possesses anti-atherogenic properties, and regulates glucose levels and fatty acid breakdown [10,11]. Low adiponectin levels are an independent risk factor for the development of metabolic syndrome [10,12] and diabetes mellitus [11,13]. Additionally, hypoadiponectinemia and adiponectin gene polymorphisms are risk factors for coronary heart disease and cardiovascular disease [14].
Cardiometabolic effects of adiponectin
2014, Best Practice and Research: Clinical Endocrinology and MetabolismCitation Excerpt :Given the critical role of T-cadherin in mediating the cardiovascular protective actions of adiponectin, future studies of the potential signaling capabilities of this complex would greatly advance this field. Genomic associations between adiponectin (Adipoq) and cardiovascular disease have been well documented [83–88]. Few studies have identified a significant cardiovascular association for AdipoR1 or AdipoR2 polymorphisms [89–92] with other studies reporting negative results [93–96].
Association of the adiponectin gene rs1501299 G>T variant, serum adiponectin levels, and the risk of coronary artery disease in a Chinese population
2012, Diabetes Research and Clinical PracticeCitation Excerpt :Therefore, the findings associated with the ADIPOQ loci may present considerable heterogeneity among different populations. In Asia, the ADIPOQ gene rs1501299 polymorphism was shown to be not only associated with type 2 diabetes [13] and cardiovascular disease [14] in Japanese patients, but also associated with metabolic syndrome in Korean subjects [15]. While this variant may not be an important determinant of type 2 diabetes mellitus or insulin resistance in another Korean population [16].
Association of polymorphisms in leptin and adiponectin genes with long-term outcomes in renal transplant recipients
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