An HphI polymorphism in the E-selectin gene is associated with premature coronary artery disease

An increased expression of E-selectin has been observed in the arterial endothelium interacting with lymphocytes and macrophages in human atherosclerotic lesions. We examined whether a polymorphism in the E-selectin gene, due to a G to T mutation (G98T) in the untranslated region of exon 2, was associated with premature coronary artery disease (CAD). Other lipid and nonlipid risk factors including a Ser to Arg (S128R) substitution in the E-selectin gene were also assessed. In patients with premature CAD (men < or = 45 years old and women < or =55 years old, N = 51) who underwent an elective diagnostic coronary arteriography, the frequency of the mutation was significantly higher than in controls (N = 50, 0.22 vs. 0.10, p = 0.024). After controlling for other CAD risk factors (plasma total cholesterol, triglyceride, LDL-apolipoprotein B. cigarette smoking and the S128R mutation) by multiple logistic analysis, the G98T mutation in the E-selectin gene was still a significant predictor of premature CAD [p = 0.022, odds ratio (95%, CI)= 3.58 (1.20-10.67)].     

Apolipoprotein E polymorphism is not associated with lipid levels and coronary artery disease in Greek patients with familial hypercholesterolaemia

Abstract Familial hypercholesterolaemia is a genetic disorder characterised by high low-density lipoprotein (LDL) cholesterol concentrations, which frequently gives rise to premature coronary artery disease (CAD). The clinical expression of familial hypercholesterolaemia is highly variable even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental and other genetic factors. Apolipoprotein E (Apo-E) has been extensively studied for its effects on the phenotype of familial hypercholesterolaemia. In this study we examined the influence of Apo-E genotype on lipid parameters and the incidence of CAD in 93 Greek patients with familial hypercholesterolaemia. Apo-E E2, E3 and E4 allele frequencies were 0.06, 0.86 and 0.09 respectively. The levels of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoproteins A and B and lipoprotein α did not differ significantly among carriers and non-carriers of the E4 allele. The prevalence of CAD and hypertension did not differ either. Our results suggest that the E4 allele is not associated with lipid levels or with the prevalence of CAD among familial hypercholesterolaemia patients of the Greek population. *The two authors were equally involved in the work     

GP78基因多态性与冠心病相关

目的探讨GP78基因多态性与冠心病的相关性。方法 Taq Man SNP基因分型法对1109例(557例冠心病患者+552例对照者)无血缘关系的研究对象进行基因分型,并应用病例对照的研究方法进行相关性分析。结果GP78基因rs2617849位点的基因分型和等位基因频率在冠心病组和对照组之间的分布存在明显差异(P0.05),冠心病组携带TT基因型(TT vs CC+CT)和T等位基因高于对照组(P0.05),在排除吸烟、高血压、糖尿病和低密度脂蛋白胆固醇等混杂因素后,仍存在显著性差异(95%CI:1.035~1.736,P0.05)。结论 GP78基因的rs2617849位点多态性与冠心病相关,rs2617849的TT基因型和T等位基因可作为冠心病易感基因标记。     

Apolipoprotein E polymorphism, age and coronary heart disease

Plasma concentrations of lipids, lipoproteins, and apolipoproteins (apo) are established risk factors for coronary heart disease (CHD). The knowledge of lipid profile may predict the potential victims of cardiovascular disease before its initiation and progression and offer the opportunity for primary prevention. The most common apo E polymorphism has been found to influence blood lipid concentrations and its correlation with CHD has been extensively investigated in the last decade. At younger ages, death from CHD is influenced by genetic factors, while the genetic effect decreases at older ages where environmental factors may play a more prominent role. If apo E polymorphism is an important genetic factor in the pathogenesis of atherosclerosis, it could affect the age of CHD onset. This review analyses the influence of apo E polymorphism on blood lipids and CHD in respect to age.     

Apolipoprotein A-I,apolipoprotein B,high-sensitivity C-reactive protein and severity of coronary artery disease in tunisian population

BackgroundThe relationship between Apolipoprotein A-I, Apolipoprotein B, C-reactive protein and the severity coronary artery disease in Tunisian CAD patients has not been examined. We investigated the association between serum ApoA-I, ApoB, hs-CRP and the severity of coronary artery disease.MethodsThis study was carried out on 180 patients who underwent angiography and 129 healthy controls. ApoA-I and ApoB as well as the serum total cholesterol, HDL, triglyceride, LDL and hs-CRP levels were measured. The ApoB/ApoA-I ratio was calculated.ResultsWe showed a decreased level of ApoA-I and an increased level of ApoB, ApoB/ApoA-I ratio and hs-CRP in CAD patients compared to the control group (P<.001). In addition, we showed a significant increase of ApoB, ApoB/ApoA-I ratio and hs-CRP in CAD patients presenting 0 to 3 vessels stenosis (P<.001). Multivariate analysis showed that ApoB (P<.001), and hs-CRP (P<.001) were independent predictors of the severity of CAD.ConclusionIn this study, ApoB and hs-CRP levels were markedly associated with the severity of CAD in Tunisian patients. We suggested that synergistic effects between dyslipidemia and inflammation led to increase the risk of the severity of CAD.     

Association of PAI-1 gene polymorphism with prognosis of coronary artery disease]

OBJECTIVE: To investigate the association of the 4G/5G polymorphism located in the promoter region of plasminogen activator inhibitor-1(PAI-1) gene with prognosis of coronary artery disease (CAD) in Chinese Hans. METHODS: One hundred and fifty five patients with CAD and 190 unrelated healthy control individuals were included in the study. The 4G/5G polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A follow-up survey of major adverse cardiovascular event (MACE) and analysis of the relationship between the severity of coronary vessels and PAI-1 gene polymorphism were carried out. RESULTS: (1) The frequency of 4G/4G genotype of PAI-1 gene was higher in CAD patients than in controls (58/155, 37.42% vs 52/190, 27.37%, P< 0.01). (2) The frequency of 4G/4G genotype of PAI-1 in patients with MACE was higher than that in patients without MACE (40/81, 49.38% vs 18/74, 23.42%; P< 0.01). (3) The frequency of 4G/4G genotype in patients with multivessel disease was higher than that in patients with single-vessel disease (30/47, 44.77% vs 9/37, 24.32%; P< 0.05). CONCLUSION: The 4G/5G polymorphism located in the promoter region of PAI-1 gene was associated with prognosis of CAD patients, and may be regarded as a biomarker of the severity of the involved vessels.     

ApoE gene polymorphism and its relationship with coronary artery disease in ethnic Kashmiri population

Apolipoprotein E is a fundamental component of various lipoproteins and plays substantial role in cholesterol/lipid transport among cells of various tissues. The ApoE gene is polymorphic with three alleles ε2, ε3, and ε4, coding for isoforms E2, E3, and E4 having different binding inclination for corresponding receptors. This work aimed to investigate the association between ApoE gene polymorphism and coronary artery disease (CAD) in Kashmiri population. APOE genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. Our study indicated ApoE ε3/ε3 to be the most common genotype in both CAD and control group. The frequency of ε2, ε3, and ε4 alleles of ApoE gene in cases was observed to be 0.06, 0.72, and 0.20, while in control subjects it was 0.075, 0.82, and 0.11, respectively. A significant difference was found between cases and controls with respect to TC, LDL, and HDL levels. Our data showed that frequency of ε4/ε4, ε4/ε3 genotype and ε4 allele was significantly higher in cases than in controls (p = 0.02, p = 0.004, p < 0.001 respectively). Moreover, the CAD patients carrying ε4 allele had significantly higher TC and LDL levels (p value <0.01). Thus our data showed a significant association of ApoE ε4 allele with the risk of CAD. The data revealed that ApoE ε4 allele is associated with increased risk of CAD and increased levels LDL and TC in Kashmiri population.     

Aging syndrome genes and premature coronary artery disease

Background  

Vascular disease is a feature of aging, and coronary vascular events are a major source of morbidity and mortality in rare premature aging syndromes. One such syndrome is caused by mutations in the lamin A/C (LMNA) gene, which also has been implicated in familial insulin resistance. A second gene related to premature aging in man and in murine models is the KLOTHO gene, a hypomorphic variant of which (KL-VS) is significantly more common in the first-degree relatives of patients with premature coronary artery disease (CAD). We evaluated whether common variants at the LMNA or KLOTHO genes are associated with rigorously defined premature CAD.     

A common variant in the ABCA1 gene is associated with a lower risk for premature coronary heart disease in familial hypercholesterolaemia

Familial hypercholesterolaemia (FH) is a common autosomal codominant hereditary disease caused by defects in the LDL receptor (LDLR) gene, and one of the most common characteristics of affected subjects is premature coronary heart disease (CHD). In heterozygous FH patients, the clinical expression of FH is highly variable in terms of the severity of hypercholesterolaemia and the age of onset and severity of CHD. Identification of mutations in the ATP binding cassette transporter 1 (ABCA1) gene in patients with Tangier disease, who exhibit reduced HDL cholesterol and apolipoprotein A1 concentrations and premature coronary atherosclerosis, has led us to hypothesise that ABCA1 could play a key role in the onset of premature CHD in FH. In order to know if the presence of the R219K variant in the ABCA1 gene could be a protective factor for premature CHD in FH, we have determined the presence of this genetic variant by amplification by PCR and restriction analysis in a group of 374 FH subjects, with and without premature CHD. The K allele of the R219K variant was significantly more frequent in FH subjects without premature CHD (0.32, 95% CI 0.27 to 0.37) than in FH subjects with premature CHD (0.25, 95% CI 0.21 to 0.29) (p<0.05), suggesting that the genetic variant R219K in ABCA1 could influence the development and progression of atherosclerosis in FH subjects. Moreover, the K allele of the R219K polymorphism seems to modify CHD risk without important modification of plasma HDL-C levels, and it appears to be more protective for smokers than non-smokers.     

Apolipoprotein E gene polymorphism and serum lipids in patients with superficial fungal disease

Superficial mycosis, including dermatophytic infections, tinea versicolor, and cutaneous candidiasis is mostly limited to the outer layers of the skin, nails, and mucous membranes. In this study, Apolipoprotein E (ApoE) polymorphism and lipoprotein cholesterol concentrations were compared between 42 patients with superficial fungal disease and 27 control subjects. Both the patients and controls were found to be normolipemic. The patients with superficial fungal disease had significantly higher concentrations of high-density cholesterol (HDL) compared to the control group (p=0.0462). However, there was no difference in the serum triglyceride, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) cholesterol concentrations. A significantly higher incidence of heterozygosity E2/3 was found in the patients (p=0.0228), and significantly lower incidence of homozygosity E3/3 in all patients, and those with candidiasis and dermatophytosis (p=0.0139, 0.0194 and 0.0337, respectively) compared to the control group. The E3/4 genotype differences between patients and controls were not statistically significant. There were slight differences in the allele frequencies between the two groups, but these did not reach statistically significant levels. It was concluded that the presence of apoE2/3 genotype, high HDL-cholesterol levels and the absence of apoE3/3 genotype can be regarded as risk factors for superficial fungal disease, especially dermatophytosis.     

Matrix metalloproteinase 13 genotype in rs640198 polymorphism is associated with severe coronary artery disease

Atherosclerosis as a main etiopathogenetic source for coronary artery disease (CAD) development is intimately related to dynamic changes in the extracellular matrix (ECM). Elevated levels of MMP-13 have been observed in human atherosclerotic plaques which could also involve variability in MMP-13 gene. The aim of the study was to associate rs640198 polymorphism with CAD and/or with its severity.The study comprised 1071 consecutive patients with suspected or known coronary artery disease (CAD), confirmed by coronary angiography.Genotyping for the rs640198 polymorphism in MMP-13 gene was performed using Taqman® assay. The TT and TG genotypes of rs640198 polymorphism in MMP-13 gene confer the significantly increased risk of triple vessel disease compared to patients without atherosclerotic lesions in coronary arteries (odds ratio = 1.64, Pcorr = 0.05). Furthermore, an increased risk of having 5 and more stenoses (odds ratio = 1.90, Pcorr = 0.004) was observed in TT and TG carriers (sensitivity of 0.613 and a specificity of 0.544; power of the test is 0.87).The T allele of MMP-13 intron polymorphism rs640198 is associated with the severity of coronary artery disease, represented by the number of affected arteries as well as by the number of stenoses confirmed by coronarography.     

Apolipoprotein B-100 gene Xba I polymorphism and cholesterol gallstone disease

The apolipoprotein (apo) B gene Xba I polymorphism is associated with alterations in serum lipids. Disturbances in serum lipids may be a risk factor for cholesterol gallstone disease. However, the relation between the Xba I polymorphism and cholesterol gallstones is unknown. This study was aimed at characterizing the polymorphism of the apo B gene Xba I in patients with gallbladder stones and the association of Xba I polymorphism with serum lipids. Xba I genotypes were measured by PCR-RFLP, and serum lipids assayed in 190 patients with gallbladder stones and 441 control subjects. The frequency of the X+/- genotype (20.63 vs. 7.94%) and X+ allele (10.79 vs. 3.97%) was significantly higher in the patient group than in the control group. Patients with the X+/- genotype had a significantly higher concentration of total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apo B in serum than patients with the X-/- genotype. The X+ allele of the apo B gene is characterized by a higher cholesterol concentration and a higher LDL-cholesterol concentration in serum, and it may be a marker for increased risk of cholesterol gallstone disease.     

冠心病患者apoE基因调控序列-219(G/T)多态性及与血脂的关系

为了研究载脂蛋白E(apoE）基因调控序列－219（G／T）多态性与人类冠心病（CHD）及其血脂水平的关系，本文采用聚合酶链反应结合了限制性片段长度多态性方法。分析了108例健康人及86例冠心病患者的－219（G／T）基因型。PCR产物直接测序验下。我们发现冠心病组apoE－219（T／T）基因型频率（0．651）和T等位基因频率（0．767）分别显著高于对照组（0．444，0．653，P＜0．05）；冠心病组和对照组T／T基因型者血清总胆固醇高于G／G基因型者。这一结果提示apoE调控区基因多态性可能影响冠心病的发生。推测apoE－219（T／T）基因型是冠心病的危险因子之一。     

Transcatheter aortic valve replacement in a patient with premature coronary artery disease and calcific aortic stenosis complicated by heterozygous familial hypercholesterolemia

We describe a case of a 59-year-old man with severe heterozygous familial hypercholesterolemia (FH) and elevated lipoprotein(a) presenting with severe aortic stenosis, treated with transcatheter aortic valve replacement (TAVR). His history also includes premature coronary artery disease requiring coronary artery bypass surgery at age 48 and a stroke at age 55. His pre-treatment lipid values include an LDL-Cholesterol (LDL-C) of 458 mg/dL, total cholesterol of 588 mg/dL, and lipoprotein (a) level of 351 nmol/L. Since his FH diagnosis, he has received several lipid-lowering agents including statins, bile acid sequestrants, nicotinic acid derivatives, and PCSK9 inhibitors. This case reflects the association of FH and elevated lipoprotein(a) with aortic stenosis and TAVR as a viable and effective treatment.     

Apolipoprotein E polymorphism and its relation to plasma lipids in coronary heart disease

Background : The present investigation is aimed at examining the Apolipoprotein E (APOE) genotypic influence on coronary heart disease (CHD) risk in northwest India (Punjab), where this disease is emerging as a major threat to public-health care system. Materials and Methods: The present study comprised of angiographically diagnosed coronary heart disease patients (n = 193) and controls (n = 150) of Punjab. Genetic polymorphism of APOE gene was investigated by polymerase chain reaction (PCR), and its association with lipid levels was evaluated. Results : The allele frequencies of epsilon2, epsilon3, and epsilon4 were 0.054, 0.795, 0.151; and 0.077, 0.856, 0.067 in patients and controls respectively. The bearers of E3/E4 genotype had threefold higher propensity of developing CHD in this population (OR, 3.04; CI, 1.55-6.25; P P P Conclusions : A significant association (P = 0.016) of epsilon4 allele, especially E3/E4 genotype, with CHD was observed, along with HDL-C and LDL-C concentrations, in the population of northwest India.