Associations of Rs3744841 and Rs3744843 Polymorphisms in Endothelial Lipase Gene with Risk of Coronary Artery Disease and Lipid Levels in a Chinese Population.
ABSTRACT: The aim of the present study was to assess the association between the 2037T/C and 2237G/A polymorphisms in the EL gene and the risk of CAD and lipid levels in a Chinese population.A case-control study including 706 patients with CAD and 315 controls was performed. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the genotypes.The EL 2037 T/C polymorphism was associated with CAD risk and HDL-C levels. No significant differences were found between the EL 2237 G/A genotypes and CAD risk and lipid levels in the whole population. However, carriers of the 2237 A allele had higher Apo A1 levels than those with the 2237 GG genotype and in the CAD subgroup (P = 0.044). The CAD cases have a significantly lower frequency of the C-G haplotypes than the controls, and the T-A haplotype was significantly more common in the CAD patients than in the controls.Our study concluded that the EL 2037 T/C polymorphism was associated with CAD risk and HDL-C levels, and that the C allele might be a protective factor against CAD in the Chinese Han population. In addition, the EL 2237 A allele might be associated with an increased Apo A1 level in CAD subjects.
Project description:Endothelial lipase (EL) plays an important role in the regulation of lipid metabolism by reducing the high density lipoprotein cholesterol (HDL-C) levels and inducing the macrophages to take up native low density lipoprotein cholesterol (LDL-C). Our purpose was to investigate the impact of EL genetic polymorphisms on the lipid-lowering effects of rosuvastatin in Chinese coronary artery disease (CAD) patients.One hundred twenty-one unrelated CAD patients, who underwent the treatment with rosuvastatin (10mg/day) for four to eight weeks, were enrolled in this study. Before and after treatment, serum lipids levels were measured. Genotypes of EL 2037T/C and 2237 G/A polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Patients with EL 2037C allele (CC?+?CT) had significantly lower LDL-C levels than those with TT genotype (CC?+?CT: 2.60?±?0.74 mmol/l; TT: 2.90?±?0.87 mmol/l; P?=?0.047), before rosuvastatin treatment. No significant differences between baseline lipid levels and the EL 2237G/A genotypes were observed. After treatment with rosuvastatin, total cholesterol (TC), high triglyceride (TG) and LDL-C levels decreased from baseline, on average, by 23.09 % (4.59?±?0.96 mmol/l to 3.47?±?0.83 mmol/l), 6.36 % (2.01?±?1.18 mmol/l to 1.68?±?1.16 mmol/l), 32.48 % (2.77?±?0.83 mmol/l to 1.79?±?0.62 mmol/l), respectively (all P?<?0.05) in all patients. While changes in HDL-C levels did not reach statistical significance. No significant effects of EL 2037T/C or 2237G/A polymorphism were observed on lipid-lowering effects of rosuvastatin.EL 2037T/C and 2237 G/A polymorphisms might not affect the lipid-owing effects of rosuvastatin in Chinese CAD patients.
Project description:Coronary artery disease (CAD) is one of the leading causes of mortality in developed countries. Adenosine triphosphate (ATP)-binding cassette A1 (ABCA1) belongs to the superfamily of membrane proteins that function as a key factor in the regulation of plasma high-density lipoprotein cholesterol (HDL-C) and the metabolism of apolipoprotein A-I (Apo AI). The role of this gene in CAD remains controversial. The aim of this study was to investigate the frequency of single-nucleotide polymorphism (SNP) rs2230806 in the ABCA1 gene of 120 CAD patients and 100 age-matched, healthy controls using restriction fragment length polymorphism and direct sequencing. Total serum cholesterol, HDL-C and serum triglyceride levels were also assayed. Low-density lipoprotein cholesterol (LDL-C) was calculated using the Friedewald formula. When compared, the G allele occurred significantly more frequently in CAD patients compared to the control subjects. The odds ratio (OR) for CAD conferred by carrying the ABCA1 G allele was 2.362 [95% confidence interval (CI) 0.9055-6.161] (P<0.08). The K variant of SNP rs2230806 in the G allele was associated with a decrease in HDL-C levels, but an increased frequency of CAD. In conclusion, the results showed that SNP rs2230806 in the ABCA1 gene is significantly associated with the incidence of CAD. Homozygosity for the G allelic variant in CAD patients may be associated with an increased risk of CAD/MI.
Project description:Previous genome-wide association studies have shown that the rs10248618 single nucleotide polymorphism (SNP) in the dynein axonemal heavy chain 11 gene (DNAH11) has been associated with serum high-density lipoprotein cholesterol (HDL-C) levels. However, little is known about such association in the Chinese population. The present study was performed to clarify the association between the DNAH11 rs10248618 SNP and serum lipid traits and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Genotypes of the DNAH11 rs10248618 SNP in 1,213 unrelated patients (CAD, 600 and IS, 613) and 631 healthy controls were determined by snapshot technology. The genotypic and allelic frequencies of the SNP were significantly different between the CAD/IS patients and the controls (P < 0.01 for all). The CT/TT genotypes and the T allele were associated with an increased risk of CAD and IS (CAD: P < 0.01 for CT/TT vs. CC and T vs. C; IS: P < 0.01 for CT/TT vs. CC and T vs. C). The CT/TT genotypes in the healthy controls, but not in CAD or IS patients, were associated with a decreased serum HDL-C and apolipoprotein (Apo) A1 concentration. These results suggest that the DNAH11 rs10248618 SNP is associated with the risk of CAD and IS in our study population. It is likely to increase the risk of CAD and IS by reducing serum HDL-C and ApoA1 levels.
Project description:BACKGROUND:Paraoxonase-1 (PON1) is an antioxidant enzyme, that resides on high-density lipoprotein (HDL). PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL. In order to evaluate the atheroprotective potential of PON1, we assessed the relationships among PON1-genotype, PON1-activity and risk of future coronary artery disease (CAD), in a large prospective case-control study. METHODOLOGY/PRINCIPAL FINDINGS:Cases (n = 1138) were apparently healthy men and women aged 45-79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n = 2237) were matched by age, sex and enrollment time. PON1-activity was similar in cases and controls (60.7+/-45.3 versus 62.6+/-45.8 U/L, p = 0.3) and correlated with HDL-cholesterol levels (r = 0.16, p<0.0001). The PON1-Q192R polymorphism had a profound impact on PON1-activity, but did not predict CAD risk (Odds Ratio [OR] per R allele 0.98[0.84-1.15], p = 0.8). Using conditional logistic regression, quartiles of PON1-activity showed a modest inverse relation with CAD risk (OR for the highest versus the lowest quartile 0.77[0.63-0.95], p = 0.01; p-trend = 0.06). PON1-activity adjusted for Q192R polymorphism correlated better with HDL-cholesterol (r = 0.26, p<0.0001) and more linearly predicted CAD risk (0.79[0.64-0.98], p = 0.03; p-trend = 0.008). However, these relationships were abolished after adjustment for HDL (particles-cholesterol-size) and apolipoproteinA-I (0.94[0.74-1.18], p-trend = 0.3). CONCLUSIONS/SIGNIFICANCE:This study, shows that PON1-activity inversely relates to CAD risk, but not independent of HDL, due to its close association with the HDL-particle. These data strongly suggest that a low PON1-activity is not a causal factor in atherogenesis.
Project description:BACKGROUND: Hyperlipidaemia is a major risk factor for coronary artery disease (CAD) and cholesteryl ester transfer protein (CETP) gene polymorphisms are known to be associated with lipid profiles. METHODS: In this study, we investigated the association of two polymorphisms in the CETP, Taq1B (rs708272) and -629C > A (rs1800775), with CAD and lipid levels HDL-C in 662 CAD + cases and 927 controls from the Singapore population comprising Chinese, Malays and Indians. RESULTS: TaqB2 frequency was significantly lowest in the Malays (0.43) followed by Chinese (0.47) and highest in the Indians (0.56) in the controls. The B2 allele frequency was significantly lower in the Chinese CAD + cases compared to the controls (p = 0.002). The absence of the B2 allele was associated with CAD with an OR 2.0 (95% CI 1.2 to 3.4) after adjustment for the confounding effects of age, smoking, BMI, gender, hypertension, dyslipidemia and diabetes mellitus. The B2 allele was significantly associated with higher plasma HDL-C levels in the Chinese men after adjusting for confounders. Associations with plasma apoA1 levels were significant only in the Chinese men for Taq1B and -629C > A. In addition, the Taq1B polymorphism was only associated with plasma Apo B and Lp(a) in the Malay men. Significant associations were only found in non-smoking subjects with BMI <50th percentile. In this study, the LD coefficients between the Taq1B and -629C > A polymorphisms seemed to be weak. CONCLUSION: The absence the Taq1B2 allele was associated with CAD in the Chinese population only and the minor allele of the Taq1B polymorphism of the CETP gene was significantly associated with higher plasma HDL-C levels in Chinese men.
Project description:L-carnitine (LC) plays an important physiologic role in lipid metabolism. To date, no clinical study has been performed to examine the effect of LC supplementation on the lipid status of coronary artery disease (CAD) patients. The aim of this study was to investigate the lipid lowering effects of LC supplementation (1000 mg/d) in CAD patients.CAD patients were identified by cardiac catheterization as having at least 50 % stenosis of one major coronary artery. Forty-seven subjects were recruited and randomly assigned to the placebo (n = 24) and to the LC (n = 23) groups. The intervention was administered for 12 weeks. The levels of LC, lipid profiles, and antioxidant enzyme activity (superoxide dismutase, SOD) were measured.The subjects in the LC group had significantly higher SOD activity (20.7 ± 4.2 versus 13.1 ± 2.9 U/mg of protein, P < 0.01), high density lipoprotein-cholesterol (1.34 ± 0.42 vs. 1.16 ± 0.24 mmol/L, HDL-C, P = 0.03), and apolipoprotein-A1 (Apo-A1, 1.24 ± 0.18 vs. 1.12 ± 0.13 g/L, P = 0.02) than those in the placebo group at week 12. Triglyceride (TG) level was slightly significantly reduced (1.40 ± 0.74 vs. 1.35 ± 0.62 mmol/L, P = 0.06) and the level of LC was negatively correlated with TG and apolipoprotein-B (Apo-B), and positively correlated with HDL-C and Apo-A1 after LC supplementation. Additionally, SOD activity was significantly negatively correlated with lipid profiles (total cholesterol, TG, and Apo-B) after supplementation.LC supplementation at a dose of 1000 mg/d showed significantly increased in HDL-C and Apo-A1 levels and a slight decrease in TG levels but no other changes in other lipids in CAD patients, and this lipid-lowering effect may be related to its antioxidant ability. Further studies should be conducted to define an optimal dose of LC for lipid-lowering in patients with CAD.Clinical Trials.gov Identifier: NCT01819701.
Project description:INTRODUCTION:The Maonan population is a relatively isolated minority in China. Little is known about endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. The present study aimed to detect the association of several LIPG SNPs and environmental factors with serum lipid levels in the Chinese Maonan and Han populations. METHODS:In total, 773 subjects of Maonan ethnicity and 710 participants of Han ethnicity were randomly selected from our previous stratified randomized samples. Genotypes of the LIPG rs2156552, rs4939883 and rs7241918 SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing. RESULTS:The allelic (rs2156552, rs4939883 and rs7241918) and genotypic (rs2156552 and rs4939883) frequencies were different between the two ethnic groups (p < 0.05-0.01). The minor allele carriers had lower apolipoprotein (Apo)A1/ApoB ratio (rs2156552 and rs7241918), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo)A1 (rs2156552) levels and higher ApoB levels (rs4939883) in the Han population, and lower HDL-C (rs2156552, rs4939883 and rs7241918) levels in the Maonan minority than the minor allele non-carriers (p < 0.0167 after Bonferroni correction). Subgroup analyses according to sex showed that the minor allele carriers had a lower ApoA1/ApoB ratio (rs2156552 and rs7241918) and higher ApoB levels (rs7241918) in Han males, and lower ApoA1 and HDL-C levels in Maonan females than the minor allele non-carriers (p < 0.0167-0.001). CONCLUSIONS:The present study demonstrates the association between the LIPG polymorphsims and serum lipid levels in the two ethnic groups. These associations might have an ethnic- and or/sex-specificity.
Project description:Maonan nationality belongs to a mountain ethnic minority in China. Little is known about the association of apolipoprotein A1 gene (APOA1) rs964184 single nucleotide polymorphism (SNP) and serum lipid levels in this population. The aim of this study was to detect the association of the APOA1 rs964184 SNP and several environmental factors with serum lipid profiles in the Chinese Maonan and Han populations.Genotypes of the APOA1 rs964184 SNP in 867 individuals of Maonan nationality and 820 participants of Han nationality were determined by polymerase chain reaction and restriction fragment length polymorphism, combined with gel electrophoresis, and confirmed by direct sequencing.The frequencies of CC, CG and GG genotypes of the APOA1 rs964184 SNP were 68.86, 29.18 and 1.96% in the Maonan population, and 63.78, 30.85 and 5.37% in the Han population (P?<?0.001). The frequency of the G allele was 16.55% in Maonan and 20.79% in Han (P?<?0.001). The G allele carriers had lower high-density lipoprotein cholesterol (HDL-C) levels in Maonan and higher triglyceride (TG) levels in Han peoples than the G allele non-carriers. Subgroup analyses showed that the G allele carriers had lower HDL-C levels in both Maonan males and females; and lower apolipoprotein (Apo) A1 levels and the ApoA1/ApoB ratio in Han males than the G allele non-carriers. Serum lipid parameters in the two ethnic groups were also associated with several environmental factors.The present study reveals that there may be a racial/ethnic- and/or gender-specific association between the APOA1 rs964184 SNP and serum lipid parameters in our study populations.Retrospectively registered.
Project description:BACKGROUND: Recent randomized controlled trials have challenged the concept that increased high density lipoprotein cholesterol (HDL-C) levels are associated with coronary artery disease (CAD) risk reduction. The causal role of HDL-C in the development of atherosclerosis remains unclear. To increase precision and to minimize residual confounding, we exploited the cholesteryl ester transfer protein (CETP)-TaqIB polymorphism as an instrument based on Mendelian randomization. METHODS: The Mendelian randomization analysis was performed by two steps. First, we conducted a meta-analysis of 47 studies, including 23,928 cases and 27,068 controls, to quantify the relationship between the TaqIB polymorphism and the CAD risk. Next, the association between the TaqIB polymorphism and HDL-C was assessed among 5,929 Caucasians. We further employed Mendelian randomization to evaluate the causal effect of HDL-C on CAD based on the findings from the meta-analysis. RESULTS: The overall comparison of the B2 allele with the B1 allele yielded a significant risk reduction of CAD (P?<?0.0001; OR?=?0.88; 95% CI: 0.84-0.92) with substantial between-study heterogeneity (I²?=?55.2%; P(heterogeneity) <0.0001). The result was not materially changed after excluding the Hardy-Weinberg Equilibrium (HWE)-violation studies. Compared with B1B1 homozygotes, Caucasian carriers of the B2 allele had a 0.25 mmol/L increase in HDL-C level (95% CI: 0.20-0.31; P <0.0001; I²?=?0; P(heterogeneity) =0.87). However, a 1 standard deviation (SD) elevation in HDL-C levels due to the TaqIB polymorphism, was marginal associated with CAD risk (OR =0.79; 95% CI: 0.54-1.03; P =0.08). CONCLUSIONS: Taken together, our results lend support to the concept that increased HDL-C cannot be translated into a reduction in CAD risk.
Project description:Polymorphisms in the cholesterol ester transfer protein (CETP) gene and apolipoprotein AI (apo AI) gene are identified as the most common genetic factors influencing high-density lipoprotein cholesterol (HDL cholesterol) levels. Low HDL cholesterol is an important risk factor for cardiovascular disease. We investigated the effect of the TaqIB polymorphism of the CETP gene and the 75G/A polymorphism of the apo AI gene on the HDL cholesterol concentration in a sample of Polish adults.A total of 621 subjects, 414 women and 207 men, were included in this study. Lipid levels were measured using standard protocols, and apolipoprotein AI was determined by immunoturbidimetric assay. CETP and apo AI genotyping was performed using a restriction fragment length polymorphism based method.Significantly lower HDL cholesterol concentrations were found in B1B1 homozygotes than in carriers of the B2 allele of the TaqIB polymorphism in the CETP gene among both men and women. In GG homozygotes of the 75G/A polymorphism in the apo AI gene lower HDL cholesterol levels were observed, but the difference did not reach statistical significance. A statistically significant association of low HDL cholesterol (< 25th percentile) with CETP genotypes was found in women (p < 0.0001) and in men (p = 0.0368).These data demonstrate a significant impact of the TaqIB polymorphism in the CETP gene on HDL cholesterol levels in the studied Polish population, while the effect of the 75G/A polymorphism in the apo AI gene appears not to be significant.