Elsevier

Atherosclerosis

Volume 220, Issue 2, February 2012, Pages 437-442
Atherosclerosis

Adiponectin G276T gene polymorphism is associated with cardiovascular disease in Japanese patients with type 2 diabetes

https://doi.org/10.1016/j.atherosclerosis.2011.11.010Get rights and content

Abstract

Objective

Adiponectin has anti-atherogenic properties and reduced serum adiponectin levels are associated with cardiovascular disease (CVD). In this study, we examined the relationship between CVD and adiponectin (ADIPOQ) gene G276T polymorphism that is associated with serum adiponectin level in a large cohort of type 2 diabetic patients.

Research design and methods

We enrolled 2637 Japanese type 2 diabetic subjects (males, 61.1%; age, 54.9 ± 7.9 years old), determined their genotypes regarding ADIPOQ G276T polymorphisms, and evaluated the association between this polymorphism and the prevalence of CVD (myocardial infarction and/or cerebral infarction).

Results

The prevalence of CVD tended to be higher as the number of G alleles increased [GG (9.5%), GT (6.8%), TT (5.6%), p value for trend = 0.0059] and was significantly higher in the subjects with GG genotype compared to those with GT or TT genotype (9.5% vs. 6.6%, p = 0.0060). Multiple logistic regression analyses revealed that the number of G alleles (Odds ratio (OR) = 1.49 with 95%CI 1.09–2.05, p = 0.0125) and GG genotype (OR = 1.66 with 95%CI 1.13–2.43, p = 0.0098) were significantly associated with CVD even after adjustment for conventional risk factors. Interestingly, the presence of obesity further and significantly increased the risk of CVD in the subjects with GG genotype (OR = 1.67 with 95%CI 1.14–2.44, p = 0.0090) but not in the subjects with TT or GT genotype (OR = 1.17 with 95%CI 0.73–1.89, NS).

Conclusions

It is likely that the G allele of the ADIPOQ G276T polymorphism is a susceptibility allele for CVD in Japanese type 2 diabetic patients, especially when they accompany obesity.

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.

Section snippets

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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