Paraoxonase-1 (PON1) activity, but not PON1(Q192R) phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population.

BACKGROUND: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that protects lipoproteins from oxidative modifications. Polymorphisms in the gene, including PON1Q192R, have been studied. However, inconsistencies regarding the above-mentioned polymorphism obscure its association with vascular disease. METHODS: Using a two-substrate (paraoxon/diazoxon) activity method, we investigated the frequencies of PON1Q192R phenotypes in 261 middle-aged subjects: 156 patients with angiographically assessed coronary heart disease (CHD) and 105 CHD-free subjects as the control group. The PON1(192) phenotype was predicted from examination of the two-dimensional plot of hydrolysis rates of diazoxon vs. paraoxon and by using the antimode of the histogram of the ratio of diazoxonase/paraoxonase activity. RESULTS: The PON1Q192R phenotype frequencies in 113 patients with occlusion >50% (coronary artery disease-positive, CAD+ group) vs. control population were as follows: QQ (0.552 vs. 0.510), QR (0.382 vs. 0.408) and RR (0.066 vs. 0.082); chi2=0.414, p=0.813. We found lower paraoxonase (POase) and diazoxonase (DZOase) activities in the CAD+ patients when compared to the control population. According to logistic regression analysis, POase activity was a better predictor of coronary disease onset compared with DZOase activity measurements and PON1Q192R phenotyping. CONCLUSIONS: We conclude that enzyme activity (within a particular phenotypic group) is more important than phenotype alone in predicting susceptibility to coronary artery disease.     

Associations between genetic polymorphisms of paraoxonase genes and coronary artery disease in a Taiwanese population

ObjectiveWe evaluated the relationship between polymorphisms of the paraoxonase (PON) gene and the risk of coronary artery disease (CAD) in Taiwanese patients.MethodsOur sample set included 369 volunteers, classified into two groups: 162 healthy volunteers and 207 CAD patients aged 60.0 ± 9.7 and 64.3 ± 12.3 years, respectively. Polymorphisms of the PON1 and PON2 genes were determined using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) techniques.ResultsThe results indicate that for the PON1 gene, the homozygous genotype RR was found significantly more often among the CAD group compared with the healthy group (OR = 1.965, 95% CI = 1.223–3.159, p = 0.005). Furthermore, for the PON2 gene, the homozygous genotype CC was found significantly more often among the CAD group compared with the control group (OR = 2.525, 95% CI = 1.103–5.780, p = 0.026).ConclusionsIndividuals homozygous for the R allele of the PON1 gene and the C allele of the PON2 gene are more likely to have an increased risk of CAD.     

Polygenetic regression model of renin-angiotensin system genes and the risk of coronary artery disease in a large angiographic population

BackgroundPolygenetic effect has rarely been addressed in the genetic studies of coronary artery disease (CAD). We used the largest and ethnically homogeneous angiographic cohort to analyze multilocus data in renin-angiotensin system genes, and provide an explicit demonstration of gene–gene interactions.MethodsA total of 1254 consecutive patients who underwent cardiac catheterization (735 with coronary artery disease and 519 without) were recruited. Angiotensin converting enzyme(ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects, adjust non-genetic confounding effects and detect gene–gene interaction between ACE and AT1R genes.ResultsWe found significant differences in global AGT gene haplotype profile and individual haplotypes between cases and controls. Significant two-way and three-way gene–gene interactions between ACE I/D, AT1R A1166C polymorphisms and AGT gene haplotypes were detected. However, subjects carrying both D allele and GGCATC haplotype had an increased risk of CAD (odds ratio = 1.63 [1.16–2.29]; P = 0.004). We also used haplotype counting to directly estimate the odds ratio of each specific AGT gene haplotype, and found that the effects of haplotypes were markedly different in subgroups with different ACE or AT1R gene genotype.ConclusionsThe regression-based haplotype analyses permits simultaneous dectection of multi-locus and multi-gene effects in determining the risk of CAD. We provide the paradigm for genetic studies of complex-trait diseases using candidate genes based on biological pathways.     

The association of ghrelin polymorphisms with coronary artery disease and ischemic chronic heart failure in an elderly Chinese population

ObjectiveTo investigate the association of coronary artery disease (CAD) and ischemic heart failure (IHF) with polymorphisms of the ghrelin gene in elderly Chinese patients.Design and methodsFifty-six patients with ischemic heart failure, sixty patients with coronary artery disease without heart failure, and one hundred healthy control subjects participated in the study. The polymorphisms were evaluated by polymerase chain reaction, sequencing, and fragment length polymorphism analysis.ResultsOnly one single nucleotide polymorphism (SNP), Leu72Met (408C/A), was observed across all samples. Gene frequencies of CC and allele frequencies of C were significantly greater in the CAD with IHF group than those in the CAD without IHF group (p = 0.025, p = 0.011). There was no significant association between the Leu72Met SNP with coronary artery disease risk factors.ConclusionOur results suggest that a C allele at position 408 of the ghrelin gene is associated with genetic susceptibility to ischemic heart failure in Chinese elders.     

Gelatinase B C(‐1562)T polymorphism in relation to ischaemic heart disease

Objective. Matrix metalloproteinases, such as gelatinase B, are important in connective tissue remodelling processes associated with atherogenesis and plaque rupture. The T allele of the gelatinase B C_(‐1562) T polymorphism has been reported to be associated with an almost 2‐fold increase in promoter activity and with the extent of coronary artery disease (CAD). The aim of this study was to analyse the relation of this gene variation to the risk and severity of CAD and the risk of myocardial infarction (MI). Material and methods. This case‐control study comprised 535 healthy controls and 2731 participants who had undergone coronary angiography. Results. In the total sample, the gelatinase B promoter polymorphism was not associated with the risk of CAD and MI or with the extent of CAD defined either by the number of diseased coronary arteries or – in patients with coronary angiography – by a score for coronary heart disease (CHD) according to the Gensini score. However, patients with TT genotype had higher CHD scores than the other genotypes in subgroups of individuals with high apolipoprotein B levels, high lipoprotein (a) plasma concentrations and high fibrinogen levels, or with combinations of increased levels of these coronary risk factors. These observations were made in the entire sample of individuals with coronary angiography and in the population of patients with documented CHD. Conclusions. Obviously, the gelatinase B C_(‐1562)T gene polymorphism is not a risk indicator for CAD and MI. With respect to the extent of CHD, the impact of this gene variation may be restricted to individuals with high apolipoprotein B, lipoprotein (a) and/or fibrinogen levels.     

Paraoxonase 1 gene polymorphisms in angiographically assessed coronary artery disease: evidence for gender interaction among Brazilians.

BACKGROUND: Paraoxonases (PON) are members of an enzyme family involved in preventing low-density lipoprotein oxidation and therefore protecting against atherosclerotic plaque formation. METHODS: We studied the Met55Leu and Gln192Arg PON1 polymorphisms in 712 patients (437 Caucasian- and 275 African-Brazilians) who underwent coronary angiography. RESULTS: Among Caucasian-Brazilians, the homozygous 55LeuLeu frequency was higher among patients with significant coronary artery disease (CAD, obstructive lesions >/=50%) than among lesion-free controls (51% vs. 30.3%; p=0.022) in females, but not in males. The Gln192Arg PON1 polymorphism was not associated with CAD, although 192GlnGln homozygotes presented lower high-density lipoprotein (HDL)-cholesterol (p=0.035) and higher triglyceride (p=0.012) levels than 192Arg allele carriers among Caucasian-Brazilian males, but not females. No other lipid-genotype association was detected. Multivariate logistic regression corrected for classic CAD risk factors shows that 55LeuLeu PON1 homozygotes were at increased CAD risk (odds ratio OR=2.852; p=0.003) and that this genotype interacted with gender in its association with CAD risk (OR=0.290; p=0.006) among Caucasian-Brazilians. CONCLUSIONS: This report shows that the 55LeuLeu PON1 genotype increases CAD risk among female Caucasian-Brazilians, irrespective of other CAD risk factors. In addition, 192GlnGln PON1 homozygotes show higher triglyceride and lower HDL-cholesterol levels in male Caucasian-Brazilians. No associations were detected among African-Brazilians.     

MEF2A基因第11外显子CAG重复序列多态性与冠心病易感性研究

目的：探讨中国上海地区汉族人群MEF2A基因第11外显子CAG重复序列多态性与其冠心病易感性的关系。方法：对300例冠心病患者（冠心病组）及100名健康体检者（健康对照组）的MEF2A基因第11外显子进行PCR扩增DNA直接测序，以检测CAG重复序列多态性，并结合临床资料进行分析。结果：2组均存在杂合性CAG重复序列，CAG重复序列数为4～11。将短CAG重复序列数（n=4～7）定义为等位基因S;长CAG重复数（n=8～11）定义为等位基因L。健康对照组中等位基因S及基因型SL频率均高于冠心病组，差异有统计学意义（P均〈0．05）。结论：MEF2A基因第11外显子CAG重复序列多态性与冠心病易感性相关，等位基因L可能是中国上海地区汉族人群的冠心病易患因素。     

An updated analysis on the association of GSTM1 polymorphism and smoking exposure with the increased risk of coronary heart disease

ObjectiveTo undertake a meta-analysis to investigate if there is an association between the glutathione S-transferase mu 1 (GSTM1) gene polymorphism, coronary artery disease (CAD) susceptibility and smoking.MethodsElectronic databases, including PubMed®, Web of Science and Embase®, were searched for relevant case–control studies. Data were extracted and the odds ratio (OR) was calculated and appropriate statistical methods were used for the meta-analysis.ResultsThe analysis included eight studies with a total of 1880 cases with CAD and 1758 control subjects. The results of this meta-analysis demonstrated that there is no association between the GSTM1 null and CAD (OR 1.24, 95% confidence interval [CI] 1.00, 1.55). An increased risk of CAD was observed in the smoking population with the GSTM1 null genotype (OR 1.48, 95% CI 1.02, 2.15). Subgroup analyses of geographical region, genotyping method and publication language category demonstrated potential relationships among gene polymorphism, smoking and CAD.ConclusionsBased on the current literature, the GSTM1 null genotype was associated to CAD in the smoking population. The interaction between smoking and GSTM1 polymorphism may contribute to the susceptibility of CAD.     

Apolipoprotein E polymorphisms in Mexican patients with coronary artery disease.

BACKGROUND: Apolipoprotein E polymorphisms have important effects on plasma lipid levels and in the genetic susceptibility to development of cardiovascular diseases. Thus, the purpose of this study was to investigate the association of apolipoprotein E polymorphisms with coronary artery disease and with plasma lipid levels in a group of Mexican Mestizo patients. METHODS: Apolipoprotein E polymorphisms were determined in 156 Mexican patients with coronary artery disease and 200 non-related healthy controls using the restriction fragment length polymorphism technique. The correlation of these polymorphisms with lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) in the patient group was determined. RESULTS: A similar distribution of allele and genotype frequencies in coronary artery disease patients and healthy controls was found. Higher serum levels of high-density lipoprotein cholesterol and lower levels of low-density lipoprotein cholesterol, triglycerides and glucose were found in patients with the APOE*2/3 genotype when compared to patients with the APOE*3/4 and APOE*3/3 genotypes, although these differences were not significant. CONCLUSIONS: Our data suggest that genetic variation at the APOE is not a genetic factor related to the genetic susceptibility to coronary artery disease in Mexican individuals, but the role of this polymorphism in determining the lipid profile cannot be excluded.     

PON1 L55M polymorphism is not a predictor of coronary atherosclerosis either alone or in combination with Q192R polymorphism in an Italian population

BACKGROUND: The present study evaluated the role of the PON1 L55M polymorphism independently and in conjunction with the Q192R polymorphism on the risk of coronary atherosclerosis in an Italian population. MATERIALS AND METHODS: Three hundred and ninety-one subjects with significant coronary stenosis (> 50%) (coronary artery disease-positive; CAD+), 196 subjects with normal coronary arteries (< 10% stenosis) (CAD-) and 178 healthy controls were screened using a combination of polymerase chain reaction and restriction enzyme digestion. RESULTS: In the pooled population, the frequencies of L and M alleles were 0.63 and 0.37, respectively; the most common haplotypes were QQ/LM (24.2%) and QR/LL (21.8%) and a strong linkage disequilibrium between L/55 and R/192 alleles was observed (D' = -0.91; P < 0.0001). CAD+ subjects did not show any significant differences in the distribution of PON1-55 genotypes as compared to CAD- subjects and population controls (chi2 = 1.5, P = 0.8). After controlling for other risk factors, the low-concentration M allele was not associated with a significant change of CAD risk (OR 1.02; 95% CI 0.80-1.29; P = 0.87). Moreover, the L55M polymorphism did not show any interaction with other risk factors such as smoking, diabetes, hypertension, low levels of high-density lipoprotein (HDL) or high ratios of low-density to high-density lipoproteins. The combination of L55M with the Q192R polymorphism did not show any effect on CAD risk. However, a marginal decrease in myocardial infarction risk was detected when QQ/MM carriers (OR 0.51; 95% CI 0.26-0.99; P = 0.048), but not LL/RR carriers, were compared with subjects not homozygous for an L or R allele. CONCLUSIONS: These findings did not indicate a major effect of the PON1 L55M polymorphism, either alone or in combination with the Q192R polymorphism, on CAD risk. Additional studies are needed for a better evaluation of the role of the 55/192 PON1 genotypes in combination on myocardial infarction risk.     

Relationship between AGT rs2493132 polymorphism and the risk of coronary artery disease in patients with NAFLD in the Chinese Han population

ObjectiveTo investigate the relationship between angiotensin (AGT) rs2493132 gene polymorphism and the risk of developing non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population.MethodsPolymerase chain reaction was performed to determine AGT genotypes. Anthropometric and clinical data were investigated and statistically analyzed in the clinical laboratory department of Qingdao Municipal Hospital.ResultsThe AGT rs2493132 CT + TT genotype was an important risk factor for CAD in patients with NAFLD and NAFLD + CAD in healthy controls. The AGT rs2493132 T allele increased the risk of NAFLD + CAD in healthy controls. The AGT rs2493132 CT + TT genotype and T allele also significantly increased the risk of CAD in patients with NAFLD after adjustments for age, sex, and body mass index. In addition, AGT rs2493132 T allele carriers showed higher total cholesterol (TC) and low-density lipoprotein (LDL) levels compared with non-carriers.ConclusionsThe AGT rs2493132 CT + TT genotype and T allele significantly increased the risk of developing CAD in patients with NAFLD in the Chinese Han population. The AGT rs2493132 T allele was associated with increased serum TC and LDL levels.     

Gender-specific effect of estrogen receptor-1 gene polymorphisms in coronary artery disease and its angiographic severity in Chinese population

BACKGROUND: The role of common polymorphisms of the estrogen receptor-1 in coronary artery disease (CAD) and it association with angiographic severity reminds conflicting in sexes and different races. METHODS: Two-hundred ten angiographically defined Chinese CAD patients and 174 control subjects were enrolled. DNA was obtained and the polymorphisms were analyzed by the polymerase chain reaction. The region containing the PvuII T/C and the XbaI A/G sites was amplified. PCR product was cleaved with the restriction endonucleases. RESULTS: No significant differences in PvuII and XbaI genotype and allele frequencies were noted between the CAD and controls.However, when stratified by gender, we noticed the PvuII genotype and allele frequencies were significantly different between CAD and controls, but in male group only, not in female group. Diabetes, hypertension, high LDL levels and the PvuII CC genotype were independent risk factors for CAD. PvuII CC was associated with the angiographic severity of CAD measuring by the number of diseased vessels as well. For XbaI, no association was found with the CAD susceptibility before and after gender stratification. CONCLUSION: This study revealed a gender-specific effect of PvuII polymorphism in Chinese CAD subjects. PvuII gene polymorphisms affect CAD susceptibility in man only. The PvuII CC is a risk factor for CAD and it is associated with angiographic CAD severity.     

BDNF Val66Met polymorphism is associated with unstable angina

BackgroundBrain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of coronary artery disease (CAD). The human BDNF Val66Met polymorphism has been shown to be associated with altered susceptibility to neuropsychiatric disorders. However it is unknown whether this polymorphism plays a role in cardiovascular disease.MethodsGenotyping of BDNF Val66Met polymorphism was carried out in 513 controls, 628 unstable angina pectoris (UAP) and 276 stable angina pectoris (SAP) patients. The plasma concentrations of BDNF and high-sensitivity C-reactive protein (hsCRP) were measured by ELISA. The general clinical data in patients and controls were obtained.ResultsThere was a significant association between genotype and allele frequency of the BDNF Val66Met polymorphism and UAP (all P < 0.05). Multivariate logistic regression analysis revealed that the BDNF_Met/Met genotype had a protective effect on the occurrence of UAP after controlling for known risk factors of CAD (OR 0.53, P = 0.005). Subjects with BDNF_Met/Met genotype also had decreased plasma hsCRP levels compared with the Val carriers (P < 0.01).ConclusionThe BDNF_Met/Met genotype has a protective effect on the occurrence of UAP, which might in part be due to the decreased plasma hsCRP level in BDNF_Met/Met carriers. To our knowledge, this is the first study that demonstrates the link between BDNF Val66Met polymorphism and CAD.     

Relation between butyrylcholinesterase K variant,paraoxonase 1 (PON1) Q and R and apolipoprotein E epsilon 4 genes in early-onset coronary artery disease

OBJECTIVES: The common K variant of butyrylcholinesterase (BChE-K), an enzyme which metabolizes acetylcholine and organophosphates, has been associated with Alzheimer's disease, especially in the presence of the apolipoprotein E epsilon 4 allele (APOE-epsilon 4). Although APOE-epsilon 4 has been associated with the development of coronary artery disease (CAD), an association between the BChE-K variant and CAD has not been explored. Paraoxonase 1 (PON1), located within HDL, is an enzyme which also metabolizes organophosphates and may be antiatherogenic. The R192 variant of PON1 (PON1-R) has been associated with CAD. DESIGN AND METHODS: To determine whether BChE-K is also associated with premature CAD, we examined the frequency of BChE-K among patients with early-onset CAD (n = 150; < 50 yr) vs. late-onset CAD (n = 150; > 65 yr) by molecular analysis. We also examined the frequency of the PON1-R allele in both groups, and explored whether there was synergism between BChE-K and APOE-epsilon 4, BChE-K and PON1-R or PON1-R and APOE-epsilon 4. RESULTS: The frequency of the BChE-K allele tended to be greater among early-onset CAD patients compared to late-onset CAD patients (41.3% vs. 31.3%; p = 0.07), but without any significant difference between males and females. There was no difference in the prevalence of the PON1-R allele between those with early- or late-onset CAD (46.0% vs. 52.7%; p = 0.25). Twenty-two patients with early-onset CAD had both the BChE-K plus APOE-epsilon 4 alleles (14.7%) compared to 11 late-onset CAD patients (7.3%) (p = 0.04). There was no such association between BChE-K and PON1-R, nor PON1-R and APOE-epsilon 4.CONCLUSIONS: Our study suggests that there is a minor association between BChE-K and early-onset CAD, especially in the presence of the APOE-epsilon 4 allele.     

The effect of apolipoprotein E gene polymorphism and Lp(a) levels on coronary artery disease with atrial fibrillation

ObjectiveTo explore the influence of apolipoprotein E (APOE) genotypes and blood lipid metabolism on coronary artery disease (CAD) with atrial fibrillation (AF).MethodsPatients with suspected CAD were consecutively enrolled and divided into groups with or without CAD and/or AF. Blood lipid levels and APOE genotypes were determined and analysed for associations with CAD and AF.ResultsA total of 2048 patients were included (400 patients without CAD or AF [controls], 126 patients without CAD but with AF, 1294 patients with CAD without AF, and 228 patients with CAD and AF). Age and lipoprotein (a) (Lp[a]) levels were significantly higher in patients with CAD and AF versus those with CAD without AF. Among patients with CAD, the E3/E3 genotype and ε3 allele frequencies were significantly lower in patients with AF than in those without AF, and the E4/E4 genotype and ε4 allele frequencies were significantly increased. Multivariate logistic regression revealed that increased Lp(a) levels and age were independent risk factors for AF in patients with CAD.ConclusionAmong patients with CAD, those with AF had increased age, ε4 frequencies and Lp(a) levels. Age and Lp(a) levels may be independent risk factors for AF in patients with CAD.     

郑州地区2型糖尿病肾功能衰竭患者芳香酯酶与基因Q192R多态性的关系

目的 探讨郑州地区汉族人群2型糖尿病慢性肾功能衰竭(DN-CRF)与血清芳香酯酶(ArE／PON1)活性及其192位基因多态性的关系。方法 通过检测2型糖尿病组(DM，121例)、DN-CRF组(123例)、健康对照组(127例)等观察对象的血清ArE／PONl活性及其192位基因多态性、血脂和脂蛋白等，进行分析研究。结果 郑州地区汉族人群中存在有ArE／PON1 192位等位基因Q与R，DN-CRF组Q、R基因频率为0．45和0．55，与DM、对照组比较，差异无统计学意义；两病例组患者血清酶活性均低于对照组，DN-CFR组降低幅度最大；DN-CFR组内RR基因型患者高密度脂蛋白胆固醇(HDL-C)、高密度脂蛋白2胆固醇(HDL2-C)水平低于QQ基因型，总胆固醇(TC)、甘油三酯(TG)和氧化型低密度脂蛋白(oxLDL)高于QQ基因型。结论 DN-CRF组ArE／PONl192位基因多态性与DM、健康对照组间虽差异无统计学意义，但不能排除DM合并DN-CRF与ArE／PON1的192位基因多态性有关；DN-CRF患者血清ArE／PON1活性降低，可能是DM合并DN的危险因素。     

The paraoxonase L55M and Q192R gene polymorphisms and myocardial infarction in a Tunisian population

ObjectivesIn the present study, we examined a possible association between the PON1 Q192R and L55M polymorphisms and myocardial infarction (MI) in a sample of the Tunisian population.Design and methodsThree hundred and ten patients with MI and 375 controls were recruited. Paraoxonase gene polymorphisms at codon 192 and 55 were analyzed by PCR-RFLP.ResultsGenotype distributions and allele frequencies of L55M were similar among the control and MI groups. For the Q192R polymorphism patients with MI had significantly higher frequency of the RR genotype compared to controls [17.1% vs. 10.9%; OR (95% CI), 1.93 (1.24–3.02); p = 0.004]. The MI patient group showed a significantly higher frequency of the R allele compared to the controls [38% vs. 30%; χ² = 10.74, p = 0.001]. The association between the PON1 Q192R polymorphism and MI remained significant after adjustment for other well-established cardiovascular risk factors.ConclusionsThe present study showed a significant and independent association between the PON1 Q192R polymorphism (presence of R allele) and MI in the Tunisian population.     

Lack of association between 27-bp repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene and the risk of coronary artery disease

The gene encoding endothelial nitric oxide synthase (ecNOS) is a candidate gene for the mediation of initial endothelial cell damage seen in arteriosclerosis. Although the association of ecNOS polymorphisms with hypertension has been studied extensively, there is little information regarding its association with coronary artery disease (CAD). We decided to study a 27 base-pair tandem repeat polymorphism in intron 4 of the ecNOS gene in 1043 individuals (413 controls, 630 patients with CAD) who consecutively underwent coronary angiography at our institution. The frequencies of the genotypes drawn from 1038 individuals were 0.69, 0.28 and 0.03 in the controls and 0.73, 0.25 and 0.02 in individulas with CAD for the ecNOS4b/b, ecNOS4b/a and ecNOS4a/a genotypes, respectively (p=n.s). There was no shift of the genotype frequencies from the expected distribution based on the Hardy-Weinberg equilibrium. Neither the rare ecNOS4a allele nor the ecNOS4a/a genotype conferred an independent risk factor for CAD in subgroups, e.g. smokers, diabetic individuals, hypertensive individuals and individuals with a low conventional risk for CAD. In five individuals we identified an additional 27-bp repeat in the ecNOS gene (ecNOS4c), which occurred heterozygous with the ecNOS4b allele (ecNOS4b/c genotype). In conclusion, the ecNOS4a allele as well as the ecNOS4a/a genotype did not show a general association with CAD in the studied European population. Even in high-risk subgroups the ecNOS4a/4a genotype did not represent an independent risk factor for CAD. In addition, the severity of CAD was not associated with the ecNOS4a allele/ecNOS4a/a genotype. Key words : Coronary artery disease; endothelium; nitric oxide; polymorphism; synthase     

Matrix metalloproteinase‐9 and paraoxonase 1 Q/R192 gene polymorphisms and the risk of coronary artery stenosis in Iranian subjects

Purpose: To investigate the association of matrix metalloproteinase‐9 (MMP‐9) and paraoxonase 1 (PON1) 192 polymorphisms with susceptibility to coronary artery stenosis (CAS) and the number of diseased vessels in patients with CAS. Methods: The study population comprised 302 unrelated Iranian individuals, including 145 patients with CAS and 157 control subjects. Genotypes for MMP‐9 and PON1 192 polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results: In our study, distributions of the TT genotype of MMP‐9 and the RR genotype of PON1 192 were significantly higher in patients compared with healthy control subjects (P<0.05). Subsequent analysis demonstrated that a significant difference existed in the male (TT+TC vs. CC and RR+QR vs. QQ, P<0.01) but not in the female. The associations of these polymorphisms with the severity of stenosis were also evaluated, which according to results distribution of MMP‐9 and PON1 192 genotypes were not significantly different compared with the severity of stenosis (P>0.05). Conclusions: The observation indicates that the polymorphisms in the MMP‐9 and PON1 192 genes potentially play a role in the manifestation of coronary atherosclerosis but does not have any effect on the number of diseased vessels in Iran. J. Clin. Lab. Anal. 24:305–310, 2010. © 2010 Wiley‐Liss, Inc.     

Association of homocysteine thiolactonase activity and PON1 polymorphisms with the severity of acute coronary syndrome

Introduction

Excess of total homocysteine (tHcy) and decrease of thiolactonase activities (HTase) have been proposed as risk factors for coronary artery diseases (CAD).

Objectives

We evaluated the relationship of tHcy and HTase with paraoxonase 1 (PON1) gene polymorphism according to CAD severity.

Design and methods

118 healthy volunteers and 91 CAD patients were compared.

Results

Serum levels of tHcy and oxidized LDL (ox-LDL) increased significantly by 26% and 48% in CAD patients and were associated with significantly lower levels of HDL cholesterol (p =  0.02) and 42% of decrease in HTase activities (p < 0.05). In these patients the HTase activity was negatively associated with tHcy and Hs CRP levels (r = − 0.622, p = 0.00 and r = − 0.355, p = 0.007 respectively) but positively associated with apoB and triglyceride levels (r = 0.35, p = 0.042 and r = 0.308, p = 0.003 respectively). HTase activity decreased inversely to the number of affected vessels and according to PON1 polymorphism. PON1 Q192R RR and PON1 L55M MM genotypes were associated with higher HTase activities. Only PON1 L55M (MM) genotype frequency was significantly higher in CAD patients than in controls (P < 0.05), while its frequency was similar between the two subgroups according to CAD severity. In a multivariate analysis, tHcy levels were the only independent factor affecting the severity of cardiovascular disease (p =  0.029).

Conclusions

High tHcy levels are associated with the severity of cardiovascular disease and may be partly explained by the diminished HTase activities in these patients.