Association Between Cholesteryl Ester Transfer Protein TaqIB Variants and Risk of Coronary Artery Disease and Diabetes Mellitus in the Population of Western Iran

Abstract

Aims: To shed light on the previously inconsistent results about the association of cholesteryl ester transfer protein TaqIB (CETP TaqIB) variants, high-density lipoprotein cholesterol (HDL-C) levels, and the risk of coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Methods: To determine the frequency of CETP TaqIB variants and to examine the possible association between CETP TaqIB polymorphism with CAD and T2DM, we studied 207 unrelated patients with CAD, 101 patients with T2DM, and 92 controls. The CETP TaqIB variants were detected by polymerase chain reaction-restriction fragment length polymorphism. Results: Logistic regression analysis indicated that the B1 allele of CETP was significantly associated with increased risk of CAD (odds ratio, OR 1.65 [95% confidence interval, CI 1.2-2.3, p=0.005]) and T2DM (OR 1.7 [95% CI 1.13-2.54, p=0.005]). Adjusted logistic regression analysis for the effects of age, sex, hypertension, diabetes, and hyperlipidemia was performed; and a significant association was found between the B1 allele and risk of CAD (OR 1.9 [95% CI 1-3.6, p=0.049]) in patients with CAD. There were no associations between the CETP alleles and the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, and HDL-C in studied groups. Conclusions: The results of the present study revealed that the CETP B1 allele is associated with increased risk of CAD and T2DM independent of plasma HDL-C level in our population.

Introduction

Cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein cholesterol (HDL-C) metabolism and maintains the cholesterol homeostasis in the body by participating in reverse cholesterol transport. It transfers cholesteryl esters from HDL-C to apolipoprotein-B containing particles in exchange for triglycerides (TGs), thereby reducing the concentration of HDL-C and increasing non-HDL-C, a lipoprotein distribution predisposing to atheroma formation (de Grooth et al., 2004; Boekholdt et al., 2005; Padmaja et al., 2009).

There are inconsistent results about the association of TaqIB polymorphism, HDL-C levels, and the risk of coronary artery disease (CAD) in the literature. Tanrikulu-Kucuk et al. (2010) among angiographically documented patients with CAD of the Turkish population reported that CETP Taq1B polymorphism neither plays a role in determining HDL-C levels nor is a useful predictor of the risk of CAD. In a Corsican population from France, no association was detected between TaqIB polymorphism and risk of CAD (Falchi et al., 2005). Chaaba et al. (2005) reported no association between CETP TaqIB gene polymorphism and CAD in patients with type 2 diabetes mellitus (T2DM). However, Kauma et al. (1996) detected an association between TaqIB polymorphism and HDL-C level in Caucasian women, whereas Durlach et al. (1999) reported that the modulating effect of TaqIB polymorphism was observed in men only. However, the results of a meta-analysis study (Boekholdt et al., 2005) indicated that the CETP TaqIB variant was associated with the risk of CAD, and this association was mediated by lower HDL-C levels. The study of Hsieh et al. (2007) among Taiwanese patients with diabetes revealed that the B1B1 genotype of CETP is a predictor of CAD in these patients. They found that patients with diabetes with the CETP B1 allele (B1B1 and B1B2) had significantly lower serum HDL-C levels compared with those with the B2B2 genotype. However, Kuivenhoven et al. (1998) and Blankenberg et al. (2003) reported an association between CETP genotype and CAD independent of HDL-C level. In two separate studies, Meguro et al. (2001) and Relvas et al. (2005) reported no association between TaqIB polymorphism and HDL-C concentration in patients with T2DM. In contrast, Kawasaki et al. (2002) reported an association between TaqIB polymorphism and HDL-C in patients with T2DM.

The population of Iran consists of different ethnic groups; Kermanshah city is located in Western Iran, and Kurds are the prominent ethnic group in the area (Rahimi et al., 2006).

Regarding the controversial results related to the role of CETP variants on the risk of CAD and diabetes, the aim of the present study was to examine the effect of CETP TaqIB variants on the risk of CAD and diabetes by determining its frequency in patients with CAD (with and without T2DM) and in patients with type 2 diabetes without CAD compared with the control group (non-CAD, nondiabetes) in the population of Western Iran.

Materials and Methods

All patients were selected from individuals who had undergone their first coronary angiography to evaluate the presence and extent of CAD. They were assessed and referred to the Cardiology Division of the Imam Ali Hospital of the Kermanshah University of Medical Sciences. Patients undergoing coronary angiography for conditions such as valvular or congenital heart disease and restrictive or dilated cardiomyopathy were excluded. Only patients undergoing elective angiography were included to avoid the influence of stress situations. Patient groups consisted of 207 CAD patients including 113 men and 94 women with the mean age of 56.9±8.6 years and 101 unrelated patients with T2DM (51 men and 50 women; mean age 56.5±9.8 years). The controls were 92 unrelated subjects (47 men and 45 women with the mean age 54.3±8.5 years). The controls consisted of nondiabetic individuals who were evaluated by angiography for suspected CAD but had normal coronary arteries (with no history of diabetes according to fasting blood sugar). Coronary angiograms were obtained with the Judkins' percutaneous retrograde femoral artery technique (Judkins, 1967) using Phillips Diagnost 5 and 35 mm films (filmed at 25 frames). All films were reviewed by two cardiologists with no previous knowledge of the condition of the patients. Coronary artery involvement was defined as ≥50% diameter obstruction of a major coronary vessel.

All patient and control groups were recruited from Imam Ali Hospital of Kermanshah University of Medical Sciences and were from a western population of Iran with Kurdish ethnic background. The diagnosis of diabetes in patients was confirmed using WHO criteria (WHO, 1999). Informed written consent was obtained from each individual before participation in the study. The study was approved by the Ethics Committee of Kermanshah University of Medical Sciences and was in accordance with the principles of the Declaration of Helsinki II.

DNA analysis

DNA was extracted from leukocytes of whole blood by the phenol-chloroform method (Old and Higgs, 1983). A 535-bp fragment in intron 1 of the CETP gene was amplified by polymerase chain reaction (PCR) using oligonucleotide primers (forward 5′-CACTAGCCCAGAGAGAGGAGTGCC-3′, reverse 5′-CTGAGCCCAGCCGCACACTAAC-3′), and PCR-amplified products were treated with 5 U of TaqIB restriction endonuclease and electrophoresed on a 2% agarose gel. The resulting fragments were 174 and 361-bp for the B1 allele and 535-bp for the uncut B2 allele (Ordovas et al., 2000).

Chemical analysis

Total plasma cholesterol (TC) and TGs were measured by the standard enzymatic method (Pars Azmon kit, Iran), using an automated RA-1000 (Technicon). The plasma low-density lipoprotein cholesterol (LDL-C) and HDL-C levels were measured using commercially available enzyme assay kits (Pars Azmon kit, Iran).

Statistical analysis

The allelic frequencies were calculated by the chromosome counting method. The genotypes and CETP allele frequencies in patients with CAD were compared to controls, and the significance of differences was calculated using the χ² test. Hardy-Weinberg equilibrium for the distribution of genotypes was performed using the χ² test. Odds ratios (OR) were calculated as estimates of relative risk for disease, and 95% confidence intervals (CI) were obtained by SPSS logistic regression software. The correlation values of plasma HDL-C, LDL-C, TG, and TC level with the CETP polymorphism between patients and controls were calculated using linear regression and an unpaired t test. A two-tailed Student's t-test was used to compare quantitative data. Statistical significance was assumed at the p<0.05 level. The SPSS statistical software package version 11.5 was used for the statistical analysis.

Results

Characteristics of patients and controls are demonstrated in Table 1. As could be seen in Table 1, the levels of TG, TC, and LDL-C were significantly higher in patients with CAD compared with controls. However, the HDL-C level was significantly lower in patients than controls. In patients with T2DM, the level of TG and LDL-C was significantly higher, and the HDL-C level was significantly lower than controls.

Table 1.

Demographical and Biochemical Parameters of the Controls and Patients

Parameters	Patients with CAD with and without diabetes (n=207)	T2DM (n=101)	Control subjects (n=92)
Age (years)	56.9±8.6	56.5±9.8	54.3±8.5
	NS
Sex (M/F)	113/94	51/50	47/45
	NS
FBS (mg/dL)	136.2±59.6, p<0.001	162.9±71.3, p<0.001	97.0±20.1
History of hypertension, %	102 (49.6), p<0.001	29 (28.7), p=0.68	24 (26.1)
LDL-C (mg/dL)	96±28, p<0.001	98.5±38.4, p<0.001	83±18
HDL-C (mg/dL)	47±9.3, p=0.007	45.2±10.2, p<0.001	49.8±5.8
TC (mg/dL)	186±42, p=0.046	185.9±45.8, p=0.09	177±26
TG (mg/dL)	177±89, p=0.038	200.8±99.3, p=0.001	156±48
BMI (kg/m²)	26±2.7	26.2±2.7	26.6±3.7
	NS	NS

Plasma HDL-C, LDL-C, TG, TC, and FBS levels and also, age and BMI were compared between patients and controls using two-tailed Student's t-test. The sex was compared between two groups by the χ²-test.

CAD, coronary artery disease; T2DM, type 2 diabetes mellitus; FBS, fasting blood sugar; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; BMI, body mass index; TG, triglyceride; TC, total cholesterol; NS, not significant p>0.05.

The distribution of CETP genotypes was in Hardy-Weinberg equilibrium among controls (χ²=1.52, p>0.1). The distribution of CETP genotypes and alleles in patients was significantly different from controls (Table 2). As demonstrated in Table 2, the frequencies of the B2B2, B1B2, and B1B1 genotypes were 2.9%, 27.5%, and 69.6%, respectively, in the total CAD group (with and without diabetes), and 21.7%, 21.7%, and 56.6%, respectively, in controls (p<0.001). In patients with CAD only, these frequencies were 1%, 29.5%, and 69.5%, respectively (p<0.001). The frequencies of the B2B2, B1B2, and B1B1 genotypes were 4%, 66.3%, and 29.7%, respectively, in the T2DM group. The allele frequencies for the B2 allele in total CAD, CAD only, T2DM, and control groups were 37.7 (p=0.005), 35.7 (p=0.004), 37.1 (p=0.011), and 50%, respectively.

Table 2.

The Distribution of Cholesteryl Ester Transfer Protein Genotypes and Alleles in Patients with Coronary Artery Disease and Diabetes and Control Subjects

	Patients with CAD with and without diabetes (n=207)	CAD (n=105)	T2DM (n=101)	Controls (n=92)
CETP genotypes
B2B2	6 (2.9%), p<0.001	1 (1%), p<0.001	4 (4%)	20 (21.7%)
B1B1	57 (27.5%), p=0.29	31 (29.5%), p=0.21	30 (29.7%)	20 (21.7%)
B1B2	144 (69.6%), p=0.028	73 (69.5%), p=0.059	67 (66.3%)	52 (56.6%)
	(χ²=28.5, DF=2, p<0.001)^a	(χ²=22.3, DF=2, p<0.001)^a	(χ²=14.2, DF=1, p=0.001)^a
B1B1+B1B2	201 (χ²=4.6, DF=1, p=0.033)^a	104 (χ²=22.2, DF=1, p<0.001)^a	97 (χ²=14, DF=1, p<0.001)^a	72
CETP alleles
B2	156 (37.7%)	75 (35.7%)	75 (37.1%)	92 (50%)
B1	258 (62.3%)	135 (64.3%)	127 (62.9%)	92 (50%)
	(χ²=8, DF=1, p=0.005)^a	(χ²=8.2, DF=1, p=0.004)^a	(χ²=6.5, DF=1, p=0.011)^a

The distribution of alleles and genotypes frequencies of CETP in patients with CAD and diabetes compared with controls were made using χ² test.

CETP, cholesteryl ester transfer protein.

The presence of B1B1 and B1B1+B1B2 genotypes was associated with 9.5-fold (95% CI 3.3-27, p<0.001) and 9.3-fold (95% CI 3.6-24.1, p<0.001), respectively, increased risk of CAD in patients with total CAD and 31 times (95% CI 3.9-250, p<0.001) and 29 times (95% CI 3.8-220, p<0.001), respectively, in patients with CAD only. In patients with T2DM, the presence of B1B1 and B1B1+B1B2 genotypes increased the risk of diabetes 7.5-fold (95% CI 2.2-25.2, p=0.001) and 6.7-fold (95% CI 2.2-20.4, p=0.001), respectively. In the total CAD and CAD only groups, the presence of the B1 allele elevated the risk of CAD 1.65-fold (p=0.005) and 1.8-fold (p=0.004), respectively (Table 3). As indicated in Table 3, the presence of the B1 allele increased the risk of diabetes 1.7 times (p=0.005). Adjusted logistic regression analysis for the effects of age, sex, hypertension, diabetes, and hyperlipidemia was performed; and a significant association was found between the B1 allele and risk of CAD with OR 1.9 (95% CI 1-3.6, p=0.049) in patients with CAD, as indicated in Table 4.

Table 3.

The Odds Ratio of Cholesteryl Ester Transfer Protein Genotypes and Alleles with Regard to B2B2 Genotype or B2 Allele in Patients with Coronary Artery Disease and Diabetes

	Patients with CAD with and without diabetes (n=207)OR (95% CI)	CAD (n=105) OR (95% CI)	T2DM (n=101)OR (95% CI)	Controls (n=92)
CETP genotypes
B2B2	Referent group (n=6)	Referent group (n=1)	Referent group (n=4)	Referent group (n=20)
B1B1	9.5 (3.3-27, p<0.001, n=57)	31 (3.9-250, p<0.001, n=31)	7.5 (2.2-25.2, p=0.001, n=30)	n=20
B1B2	2.25 (2.5-21, p<0.001, n=144)	1.14 (3.8-220, p=0.35, n=73)	6.4 (2.1-20, p=0.001, n=67)	n=52
B1B1+B1B2	9.3 (3.6-24.1, p<0.001, n=144)	29 (3.8-220, p<0.001, n=104)	6.7 (2.2-20.4, p=0.001, n=67)	n=72
CETP alleles
B2	Referent group (n=156)	Referent group (n=78)	Referent group (n=75)	Referent group (n=92)
B1	1.65 (1.2-2.3, p=0.005, n=258)	1.8 (1.2-2.7, p=0.004, n=129)	1.7 (1.1-2.5, p=0.005, n=127)	n=92

OR as estimates of relative risk for disease were calculated, and 95% CIs were obtained by using χ² regression binary logistic analysis.

CI, confidence interval; OR, odds ratio.

Table 4.

The Odds Ratio of Presence Cholesteryl Ester Transfer Protein B1 Allele with Regard to B2 Allele in Patients with Coronary Artery Disease Compared with Controls After Adjusting for Sex, Age, Normolipidemia, Absence of Diabetes, and Hypertension

	Patients with CAD OR (95% CI)	Control subjects
CETP alleles
B2	Referent group (n=21, 30.9%)	Referent group (n=48, 45.7%)
B1	1.9 (1-3.6, p=0.049, n=47, 69.1%)	n=57, 54.3%
	χ²=3.9, DF=1, p=0.049

OR as an estimation of relative risk for disease were calculated, and 95% CI was obtained by using χ² regression binary logistic analysis.

Plasma concentrations of TG, TC, LDL-C, and HDL-C in the presence of B1 and B2 alleles were compared between patients and controls. Both patients with total CAD and those with CAD only with the B1 or B2 allele had significantly higher levels of LDL-C compared with controls with the same alleles. HDL-C level in patients with total CAD with B1 allele was significantly (p<0.001) lower than in controls with the same allele (Table 5). The concentration of TG was significantly higher in patients with total CAD with the B1 allele compared with controls with the same allele. However, in CAD only patient carriers for the B2 allele, the TG concentration was significantly lower than in controls with this allele. Patients with T2DM with the B1 allele had significantly higher levels of LDL-C and TG compared with control carriers of the B1 allele. However, in T2DM carriers of the B2 allele only, HDL-C level was significantly lower than in controls with the same allele. When lipids levels in carriers of the B1 allele were compared with those with the B2 allele in each group of patients, we found a non-significant higher level of LDL-C (2.5%) and nonsignificant lower level of HDL-C (around 2.7%) in patients with total CAD carrying the B1 allele. The LDL-C and TC levels tended to be higher (around 9% and 4%, respectively) in T2DM patients carriers of the B1 allele compared with carriers of the B2 allele. In contrast, in controls, the presence of the B1 allele was concomitant with significantly higher levels of HDL-C and lower levels of TG compared with carriers of B2 allele (Table 5).

Table 5.

The Comparison of Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, Total Cholesterol, and Triglyceride Levels Between Cholesteryl Ester Transfer Protein Genotypes (B2B2, B1B1, or B1B2) and Alleles in Patients with Coronary Artery Disease, Total Coronary Artery Disease, and Type 2 Diabetes Mellitus Compared with Control Subjects

	CAD	Patients with CAD with and without diabetes	T2DM	Controls
B2B2	n=1	n=6	n=4	n=20
LDL-C (mg/dL)	94 (p=0.58)	83.2±14^a (p=0.9)p=0.26^b	72±20.7^a (p=0.4)p=0.15^b	82±21p=0.84^b
HDL-C (mg/dL)	56 (p=0.24)	49.8±5.5^a (p=0.73)p=0.45^b	42±3.55^a (p=0.034)p=0.52^b	48.9±5.8p=0.42^b
TC (mg/dL)	197 (p=0.44)	176±22.8^a (p=0.95)p=0.53^b	160±29.43^a (p=0.33)p=0.25^b	175±27p=0.71^b
TG (mg/dL)	123 (p=0.26)	157±55^a (p=0.58)p=0.58^b	230±66.8^a (p=0.47)p=0.55^b	192±95p=0.21^b
B1B1+B1B2	n=104	n=201	n=97	n=72
LDL-C (mg/dL)	94±26 (p=0.002)	96±29 (p<0.001)	100±38.6^a (p=0.001)	83±17
HDL-C (mg/dL)	49.1±7.5 (p=0.34)	46.9±9.4 (p=0.008)	45.3±10.4^a (p=0.001)	50.1±5.8
TC (mg/dL)	183±36 (p=0.28)	187±43 (p=0.08)	187±46.2^a (p=0.1)	177±26
TG (mg/dL)	152±84 (p=0.95)	177±90 (p=0.029)	200±100.4^a (p<0.001)	153±51
B1 allele
LDL-C (mg/dL)	94±26.9^a (p=0.001)p=0.96^b	96.8±29.6^a (p<0.001)p=0.39^b	102±38^a (p<0.001)p=0.14^b	83.1±17p=0.81^b
HDL-C (mg/dL)	49±7.6^a (p=0.065)p=0.6^b	46.5±9.6^a (p<0.001)p=0.17^b	45.2±10.5^a (p<0.001)p=0.95^b	50.8±5.8p=0.025^b
TC (mg/dL)	182±36.3^a (p=0.32)p=0.87^b	186±42.7^a (p=0.08)p=0.94^b	189±45^a (p=0.2)p=0.3^b	178±26.2p=0.59^b
TG (mg/dL)	154.9±83.8^a (p=0.33)p=0.46^b	177±90^a (p=0.001)p=0.93^b	201±103^a (p<0.001)p=0.99^b	145±50.6p=0.001^b
B2 allele
LDL-C (mg/dL)	94.2±24 (p=0.001)	94.4±26.3 (p<0.001)	93±39 (p=0.063)	82.5±18.6
HDL-C (mg/dL)	49.6±7.1 (p=0.47)	47.8±8.9 (p=0.31)	45.3±9.7 (p=0.027)	48.6±5.6
TC (mg/dL)	183.2±35.7 (p=0.12)	186.4±41.6 (p=0.029)	182±47 (p=0.75)	176±25.3
TG (mg/dL)	146±82 (p=0.009)	176±88.4 (p=0.9)	201±92 (p=0.26)	177.5±72.4

The correlation values of plasma HDL-C, LDL-C, TG, and TC levels with CETP polymorphism between patients and controls were calculated using t-test analysis.

Comparison has been made between patients and controls.

Comparison has been made between B1 and B2 allele within each group.

Also, Post-hoc analysis was performed to compare the distribution of parameters between patients with total CAD and those with T2DM. No significant difference was found related to the distribution of genotypes and alleles between the two groups. However, in patients with T2DM with the B2B2 genotype, the level of HDL-C was significantly (p=0.037) lower compared with patients with total CAD with the same genotype. Also, TG level tended to be higher (p=0.053) in patients with T2DM with the B1B1+B1B2 genotype compared with patients with total CAD with the same genotype.

Discussion

CAD and T2DM are complex disorders in which both genetics and environmental factors play an important role in pathogenesis (Felehgari et al., 2011). The genetic contribution appears to differ considerably between different populations and under different environments (Liu et al., 2007). The genetic factors include DNA polymorphism in the genes affecting lipid metabolism (Isbir et al., 2003). TaqIB polymorphism in the CETP gene has been reported to be associated with plasma levels of HDL-C (Isbir et al., 2003). In the present study, we observed a significant association between the B1 allele of CETP with the risk of CAD with OR=1.65 and OR=1.8 in patients with total CAD and those with CAD only, respectively. This association remained after adjusting for normolipidemia, absence history of diabetes, and hypertension among patients with CAD with OR=1.9. No significant difference was observed between HDL-C levels in various genotypes of CETP and also between the B1 and B2 alleles among patients and controls. It seems that the influence of the B1 allele on the risk of CAD is independent of HDL-C level in our population. Some studies reported that TaqIB polymorphism was associated with the incidence of CAD. Nevertheless, other studies did not detect such correlation, and some studies supported the hypothesis of a CETP effect independent of HDL-C levels. An association of CETP TaqIB gene polymorphism with CAD in a Taiwanese population with T2DM has been reported (Hsieh et al., 2007). Among the Turkish population, CETP TaqIB gene polymorphism was associated with the risk of CAD and lower HDL-C level in both patients with CAD and controls (Yilmaz et al., 2005). However, in two other studies from Turkey, the TaqIB polymorphism was not associated with HDL-C level or risk of CAD among angiographically documented patients with CAD (Tanrikulu-Kucuk et al., 2010) and was not correlated to HDL-C in healthy individuals (Dogru-Abbasog et al., 2009). Also, Chaaba et al. (2005) reported no association between TaqIB polymorphism and CAD in T2DM. A meta-analysis by Boekholdt et al. (2005) suggested a relationship between TaqIB genotype and CAD risk that is mediated by HDL-C level. However, a relationship between CETP genotype and CAD independent of HDL-C level has also been reported (Kuivenhoven et al., 1998; Blankenberg et al., 2003). In the study of Blankenberg et al. (2003), it was shown that the mechanism of influence of CETP genotype on cardiovascular risk appeared rather independent of HDL-C and CETP concentrations. Also, they speculated that the impact of genotype on risk of CAD is rather mediated by a local effect of CETP within the vessel wall. Many factors, such as ethnic origin, diet, and culture, can influence the association between CETP polymorphism and HDL-C concentration. Further, Kuivenhoven et al. (1998) reported that among Dutch men with established CAD, the TaqIB polymorphism of the CETP gene is associated with the progression of coronary atherosclerosis. This relation was dose dependent and independent of HDL-C concentrations and plasma lipase activity. Also, no association between the TaqIB polymorphism of the CETP gene and lipid level in obese and nonobese individuals has been reported (Srivastava et al., 2008). In contrast, recently in Caucasian patients with acute coronary syndrome, patients homozygous for the B2 allele and nonusers of statins had a strong increase of recurrent cardiovascular events (Pillois et al., 2009).

Results of the present study revealed that the B1 allele of CETP is significantly associated with the increased risk of CAD in individuals with or without diabetes. However, the relative risk of CAD in the presence of CETP variants in our patients was found to be independent of plasma HDL-C level.

We found a significantly higher frequency of B1B1 and B1B2 genotypes among patients with T2DM with OR 7.5 (95% CI 2.2-25.2) and OR 6.4 (95% CI 2.1-20), respectively, compared with controls. No significant difference was observed between HDL-C levels in various genotypes of CETP among patients and controls. It seems that the influence of B1B1 and/or B1B2 genotype on the risk of diabetes is independent of HDL-C level in our population. There have been inconsistent results from numerous studies regarding the relationship between CETP genotype and HDL-C levels in patients with diabetes. Our results are similar to the study of Meguro et al. (2001) and Kakko et al. (2001), who did not report an association between CETP TaqIB and HDL-C level. In contrast, it has been suggested that due to the association of the B2 allele with higher HDL-C level, the protective effect of the B2 allele is through the higher HDL-C level (Kauma et al., 1996). Further, Kawasaki et al. (2002) reported an association between TaqIB polymorphism and HDL-C level in patients with T2DM.

In the present study, we detected no association between history of blood pressure and various genotypes of CETP. In the study of Porchay-Balderelli et al. (2007), similar to ours, the TaqIB polymorphism was not associated with a history of high blood pressure.

In summary, we detected that the B1 allele of CETP significantly increased risk of CAD which was independent of plasma HDL-C level in our sample from Western Iran. Also, we found an association between a CETP variant and diabetes in the same population. This observation emphasizes the importance of geographical location and ethnic background of subjects in the study of CETP variants and their association with CAD and T2DM. Therefore, additional analysis is needed to clarify the true contribution of the CETP variants to the development of CAD and diabetes in different world populations.

Footnotes

Acknowledgment

This work was financially supported by a grant from Vice Chancellor for Research of Kermanshah University of Medical Sciences, Kermanshah, Iran.

Disclosure Statement

All authors disclose any commercial associations that might pose a conflict of interest in connection with the submitted article. No competing financial interests exist for all authors.

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