Relationship Between TaqIB Cholesteryl Ester Transfer Protein Gene Polymorphism and Macrovascular Complications in Japanese Patients With Type 2 Diabetes

Abstract

Cholesteryl ester transfer protein (CETP) is a key regulating factor of lipid metabolism, and the polymorphism of its gene may therefore be a candidate for modulating the lipid parameters, altering the susceptibility to atherosclerosis in type 2 diabetic subjects. In a group of 443 unrelated Japanese patients with type 2 diabetes, we studied the B1B2 polymorphism at the CETP locus, which is detectable with the restriction enzyme TaqI. Patients were separated into three groups according to genotype and compared based on their clinical characteristics, lipid parameters, and macrovascular complications. The B2 allele was associated in a dose-dependent fashion with higher HDL cholesterol and apolipoprotein AI levels, together with lower CETP concentrations. Furthermore, the prevalence of macrovascular complications, such as coronary heart disease, arteriosclerosis obliterans, and cerebral vascular disease, was significantly higher in subjects with the B1B1 genotype. Multiple logistic regression analysis also showed that the B1 allele of CETP genotype was associated with the incidence of these three complications independently of other risk factors. Thus, in type 2 diabetic patients, the B1B2 polymorphism of CETP gene is likely to be a strong genetic predictor of macrovascular complications. Diabetes 51:871-874, 2002 T ype 2 diabetic patients are at high risk of atherosclerotic diseases, such as coronary heart disease (CHD), cerebral vascular disease (CVD), or arteriosclerosis obliterans (ASO) (1). This increased risk can be partly accounted for by the lipoprotein disorders linked to insulin resistance: elevated VLDL, triglycerides, and cholesterol, together with low HDL cholesterol (2). The inverse relationship between the level of HDL cholesterol and the risk of cardiovascular disease is commonly explained by the crucial role of HDL in reverse cholesterol transport (3-5). By this process, cholesterol from peripheral cells is taken up by HDL and transported to the liver, where it is metabolized and excreted in the bile. Cholesteryl ester transfer protein (CETP) has a central role in the metabolism of HDL lipoprotein and may therefore alter the susceptibility to atherosclerotic vascular disease (3). In a normolipidemic population, the plasma CETP concentration varies mostly over a threefold range and is influenced by environmental factors (6). Plasma CETP has been shown to be elevated in smokers and to be decreased by heavy alcohol drinking and physical training (7-9).Recently, the B1B2 polymorphism of intron 1 of the CETP gene (presence or absence of a TaqIB restriction site) was shown to be a determinant of HDL cholesterol (10). It has been reported that both healthy and type 2 diabetic subjects with the B2B2 genotype of TaqIB polymorphism have significantly higher HDL cholesterol levels than those with the B1B1 or B1B2 genotype (11,12). Furthermore, in subjects with the B2B2 genotype, the progression of coronary atherosclerosis is more greatly suppressed by pravastatin than in those with the B1B1 or B1B2 genotype,...

Association of the CETP TaqIB Polymorphism with Coronary Artery Disease in Type 2 Diabetic Patients

“…Some population-based studies have examined the relationship between TaqIB polymorphism and the risk of CAD in diabetic patients, but the reported results have been inconsistent (19,25,29). For example, two previous studies reported a relationship between TaqIB polymorphism and macrovascular complications of diabetes (29,35), while according to Chaaba (36), there is no correlation between this polymorphism and CAD in type 2 diabetic patients, which is in line with our study. It is still unknown how CETP isoforms could lead to the development of CAD in diabetic individuals.…”

Studies of the CETP TaqIB and ApoE Polymorphisms in Southern Thai Subjects with the Metabolic Syndrome

“…In type 2 diabetic patients, the B2 allele was associated in a dose-dependent fashion with higher HDL-C and lower CETP concentrations. Then, the prevalence of macrovascular complications was significantly higher in subjects with the B1B1 genotype (Kawasaki et al 2002). In Turkey, B1B1 genotype had higher in diabetic patients with myocardial infarction than diabetic patients without myocardial infarction (Yilmaz et al 2004).…”

“…The B1 allele is associated with low HDL-C levels and increased CETP levels and activity (Kuivenhoven et al 1997), whereas B2 allele is associated with a decreased risk of CVD (Ordovas et al 2000;Liu et al 2002) and MetS (Ozsait et al 2008). B1 allele has been shown to influence development of Alzheimer's disease and type 2 diabetes mellitus (Fidani et al 2004;Kawasaki et al 2002;Yilmaz et al 2004). Moreover, the association of B1 allele with MetS has been reported (Ozsait et al 2008;Sandhofer et al 2008;Elsammak et al 2011).…”

Cholesteryl ester transfer protein B1B1 genotype as a predictor of coronary artery disease in Taiwanese with type 2 diabetes mellitus

“…The relationship between the TaqIB genotype and the risk of CAD in diabetes has been investigated in some population-based studies, albeit without consistent results [26][27][28]. Two previous studies [26,27] revealed CETP TaqIB gene polymorphism to be associated with macrovascular complications of diabetes. However, Chaaba et al [28] reported that there was no association between CETP TaqIB gene polymorphism and CAD in type 2 diabetes mellitus.…”