A lack of association between adiponectin polymorphisms and coronary artery disease in a Chinese population

We investigated the association between two single nucleotide polymorphisms (SNPs) in the adiponectin gene (rs822395 and rs266729) and coronary artery disease (CAD) in a case-control study of 198 unrelated Chinese CAD patients (with ≥ 70% coronary stenosis or previous myocardial infarction) and 237 non-CAD controls. The ligase reaction was used to detect SNPs rs822395 and rs266729, and the allelic association of these SNPs with the occurrence and severity of CAD was assessed. There were no significant differences in the genotypic or allelic frequencies of the two SNPs between control and CAD individuals. In addition, there was no association between the two SNPs and the severity of CAD based on the number of diseased vessels. The frequencies of alleles C and G at rs266729 differed significantly between females in the CAD and control groups, but not between males. Female carriers of allele G at rs266729 had a higher risk of CAD compared with allele C carriers (OR = 1.30, 95% CI: 1.09-2.64, p = 0.02). These results indicate a gender-specific effect of the adiponectin gene rs266729 variant in modulating the risk of CAD in women.     

ADRB2 polymorphisms predict the risk of myocardial infarction and coronary artery disease

Recently, the rs1042713 G > A and rs1042714 C > G polymorphisms in the beta-2adrenergic receptor (ADRB2) gene were shown to be related to atherosclerosisdiseases. Therefore, we performed a systemic meta-analysis to determine whether thetwo functional polymorphisms are related to the risk of myocardial infarction (MI)and coronary artery disease (CAD). We identified published studies that are relevantto our topic of interest. Seven case-control studies, with a total of 6,843 subjects,were incorporated into the current meta-analysis. Our analysis showed a higherfrequency of rs1042713 G > A variant in patients with MI or CAD compared tohealthy controls. A similar result was also obtained with the rs1042714 C > Gvariant under both the allele and dominant models. Ethnicity-stratified subgroupanalysis suggested that the rs1042714 C > G variant correlated with an increasedrisk of the two diseases in both Asians and Caucasians, while rs1042713 G > A onlycontributes to the risk of two diseases in Asians. In the disease type-stratifiedsubgroups, the frequencies of both the rs1042713 G > A and rs1042714 C > Gvariants were higher in the cases than in the controls in both the MI and CADsubgroups. Collectively, our data contribute towards understanding the correlationbetween the rs1042713 G > A and rs1042714 C > G polymorphisms inADRB2 and the susceptibility to MI and CAD.     

Common gene polymorphism in ATP-binding cassette transporter A1 and coronary artery disease: A genetic association study and a structural analysis

ATP-binding cassette transporter A1 (ABCA1) has a crucial role in removing intracellular cholesterol and plays a protective role against atherosclerosis. Therefore, genetic polymorphisms in this gene may alter the susceptibility to coronary artery disease (CAD). This study was aimed to examine the association of rs2230806 (c.1051 G > A; p.R219K) variation in the ABCA1 gene with CAD in a case-control design which was followed by a meta-analysis and in silico approach. In the case-control study, 300 subjects including 150 individuals with CAD and 150 healthy controls were recruited. The c.1051 G > A genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. In the meta-analysis, eligible studies were collected from PubMed, Google Scholar, and ScienceDirect databases and pooled odds ratio, heterogeneity, publication bias, and sensitivity analyses were carried. Finally, some bioinformatics tools were employed to assess the impacts of p.R219K variation on ABCA1 protein structure. Our case-control examination showed a statistically significant association between c.1051 G > A genetic polymorphism and CAD risk. In addition, the meta-analysis showed reliable significant associations between c.1051 G > A transition and risk of CAD in the Caucasian population. In silico analysis showed that the p.R219K substitution could alter the secondary structure, hydrophobicity pattern, and Ramachandran plot of ABCA1. These findings elucidate that the c.1051 G > A variation could be a genetic risk factor for CAD and it could be considered as a prognostic and predictive biomarker for susceptible individuals.     

Myeloperoxidase gene-463G > A polymorphism and premature coronary artery disease

We investigated the association between myeloperoxidase gene -463G > A polymorphism and premature coronary artery disease (CAD) in two Chinese population samples: 229 patients and 230 controls. Genotypes were determined by ligase detection reaction-polymerase chain reaction sequencing and the grouping technique. We found lower frequencies of both the A/A genotype and the A allele in patients (p < 0.05). Multivariate logistic regression showed that the risk of premature CAD in subjects carrying the AA genotype was reduced by 83% in relation to individuals carrying the G/G genotype (OR = 0.172, 95% CI: 0.057-0.526, p = 0.002). Our results indicate that -463G > A polymorphism of the myeloperoxidase gene is associated with premature CAD in Chinese individuals, suggesting that the AA genotype is a protective factor against premature CAD.     

Association between rs10118757(A/G) in methylthioadenosine phosphorylase gene and coronary artery disease in Chinese Hans

Studies focusing on the association of gene methylthioadenosine phosphorylase (MTAP) with the risk of coronary artery disease (CAD) and myocardial infarction (MI) are limited.     

MPO129A／G基因多态性与冠心病严重程度相关研究

目的：探讨髓过氧化物酶129A／G基因多态性与冠心病严重程度关系。方法：入选住院冠心病患者267例,均行冠脉造影检查。用比色法测定血清髓过氧化物酶活性;用聚合酶链反应．限制性片段长度多态性（PCR-RFLP）确定各研究对象的基因型。根据冠脉造影结果分别采用冠脉病变支数和Gensini评分来评估冠心病严重程度。结果：MPO129位点A、G等位基因频率分别为0．107和0．893。不同基因型组间血清髓过氧化物酶活性无明显差异,不同基因型在Gensini评分组间的分布无明显差异,基因型GG患者冠脉病变倾向于多血管病变。结论：髓过氧化物酶129A／G基因多态性与血清髓过氧化物酶活性无显著相关,其不能作为预测冠心病病变严重程度的理想指标。     

A preliminary study of human paraoxonase and PON 1 L/M55–PON 1 Q/R 192 polymorphisms in Turkish patients with coronary artery disease

Paraoxonase 1 (PON 1) is a high‐density lipoprotein (HDL)‐associated enzyme with antioxidant function protecting low‐density lipoprotein (LDL) from oxidation. PON 1 has two amino acid polymorphisms in coding region; L/M 55 and Q/R 192. These polymorphisms modulate paraoxonase activity of the enzyme. PON 1 activity decreases in coronary artery disease (CAD). In the present study, distribution of PON 1 L/M 55 and Q/R 192 polymorphisms and the effect of these polymorphisms on the activities of PON 1, and on the severity of CAD in 277 CAD (+) patient and 92 CAD (?) subjects were examined. PON 1 L/M 55 and Q/R 192 genotypes were determined by PCR, RFLP and agarose gel electrophoresis techniques. Genotype distributions and allele frequencies for PON 1 Q/R 192 polymorphism were not significantly different between controls and CAD (+) patient group (p > 0.05), but in genotype and allele distribution of PON 1 L/M55 polymorphism, there was significantly difference among groups (p < 0.05). Genotype distributions for both polymorphisms were not significantly different between subgroups of single‐vessel disease (SVD), double‐vessel disease (DVD) and triple‐vessel disease (TVD). Serum PON 1 activity was lower in CAD (+) group than in controls and this was also statistically significant (p < 0.001). In both groups, the highest PON activities were detected in LL and RR genotypes. In summary, our results suggest that there is an association between the PON 1 L/M 55 polymorphism of paraoxonase and CAD in Turkish patients but not with PON 1 Q/R 192 polymorphism. However, it is hard to correlate these polymorphisms and severity of CAD. Copyright © 2009 John Wiley & Sons, Ltd.     

Association of polymorphisms in the chemokine receptor CX3CR1 gene with coronary artery disease

Two chemokine receptor CX3CR1 gene variants, V249I and T280M, have been implicated in coronary artery diseases (CAD). Currently no consistent effect has been revealed and their role in cardiovascular disease is still conflicting. In the present study the association of CX3CR1 genotypes with CAD and myocardial infarction (MI) was investigated in the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort, including 3316 individuals in whom cardiovascular disease angiographically has been defined or ruled out. Similarly to previous studies, the alleles I249 and M280 were in strong linkage disequilibrium and formed an I₂₄₉M₂₈₀ haplotype. However, there was no relationship between CX3CR1 genotypes or corresponding haplotypes and the prevalence of CAD or MI. Adjusted for classical risk factors (age, sex, hypertension, dyslipidemia, diabetes mellitus and smoking), the odds ratio (OR) of V249I for CAD was 0.95 (95% confidence interval (CI) = 0.78–1.15, p = 0.61). The OR of T280M for CAD was 0.83 (95% CI = 0.66–1.04, p = 0.11). Furthermore, CX3CR1 variants were not associated with C-reactive protein levels, age at onset of CAD, severity of CAD and MI. In conclusion, present data of LURIC do not support the hypothesis that common variants of the CX3CR1 gene are associated with the presence of CAD or MI.     

ALDH2 gene G487A polymorphism and coronary artery disease: a meta‐analysis including 5644 participants

Several studies indicate the mitochondrial Aldehyde Dehydrogenase‐2 (ALDH2) gene G487A polymorphism may be correlated with coronary artery disease (CAD) susceptibility, but a clear consensus has yet to be reached. To elucidate the relationship between the ALDH2 gene G487A polymorphism and CAD within the Chinese population, a meta‐analysis of 5644 subjects from nine individual studies was performed. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals were assessed using random or fixed‐effect models depending the heterogeneity existence or not. Our meta‐analysis found a significant association between ALDH2 gene G487A polymorphism and CAD in the Chinese population under allele (OR: 1.830, 95% CI: 1.560–2.140, P = 1.36 × 10^?13), recessive (OR: 1.920, 95% CI: 1.530–2.390, P = 1.20 × 10^?8), dominant (OR: 1.593, 95% CI: 1.336–1.900, P = 2.22 × 10^?7), homozygous (OR: 2.280, 95% CI: 1.810–2.870, P = 3.17 × 10^?12) and heterozygous genetic models (OR: 3.330, 95% CI: 2.070–5.370, P = 7.81 × 10^?7). The positive correlation between the ALDH2 gene G487A polymorphism and CAD makes the mutation a strong candidate as a genetic risk marker for CAD. Through further analysis, we also found that A allele carriers of ALDH2 gene G487A polymorphism may be particularly susceptible to CAD.     

The association of MDR1 C3435T and G2677T/A polymorphisms with plasma platelet-activating factor levels and coronary artery disease risk in Turkish population

Increased levels of peripheral proinflammatory mediators can contribute to the development of coronary artery disease (CAD). Platelet activating factor (PAF) is an important proinflammatory mediator and plasma levels of PAF correlate with transmembrane transporter multidrug resistant 1 P-glycoprotein (MDR1 Pgp) expression and activity. MDR1 polymorphisms can affect the expression and activity of Pgp and plasma PAF levels. Therefore, we investigated the possible relationship between MDR1 C3435T and G2677T/A polymorphisms and plasma PAF levels and the risk of CAD. The study population consisted of 198 patients angiographically documented CAD, including 113 cases with at least 1 coronary artery with ≥ 50% luminal diameter stenosis and 85 control subjects with strictly normal coronary angiograms. Genotypes of the MDR1 C3435T and G2677T/A polymorphisms were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Plasma PAF levels were detected by enzyme-linked immunosorbent assay (ELISA). There were no significant differences among plasma PAF levels in regard to MDR1 C3435T and G2677T polymorphisms in CAD patients and controls. No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in the MDR1 gene between the patients and the control subjects. Furthermore, analysis of MDR1 haplotypes did not show any associations with increased plasma PAF levels and risk of CAD. Our results suggest that plasma PAF levels are not associated with MDR1 gene polymorphisms. There is no association between MDR1 C3435T and G2677T/A polymorphisms and the risk of CAD in Turkish patients.     

Association of CYBA G640A variation with coronary artery disease in Indians

Introduction: Oxidative stress induces atherosclerosis by triggering an inflammatory cascade within the vascular wall.

Objective: To investigate the role of pro-oxidant and antioxidant gene variations with CAD in Indian subjects.

Materials & methods: It’s a case-control study and genotyping for the variants MPO G-463A, CYBA G640A, SOD2 Val16Ala and CAT C-262T were performed by conventional PCR techniques.

Results: Only CYBA G640A variant allele was found to be significantly (p?=?0.0075) associated with CAD.

Conclusion: Although CYBA G640A variation was found to be significant, a larger study is needed to validate these results and establish its role as a biomarker.     

C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease

Elevated levels of homocysteine is a risk factor for coronary artery disease. The C677T transition in methylenetetrahydrofolate reductase (MTHFR) is associated with increased homocysteine levels in the general population. We analysed the association between the MTHFR C677T polymorphism and serum homocysteine concentrations in patients with coronary artery disease (CAD). Allele frequencies for the 'C' (wild-type) and 'T' alleles were 0.71 and 0.29 in CAD patients and 0.70 and 0.30 in controls, respectively. There was no difference in the distribution of MTHFR genotypes between patients with CAD and control subjects (p > 0.05). In the patient group, homocysteine levels were higher than controls but not significantly (13.99 +/- 7.44 vs. 11.77 +/- 5.18 micromol l(-1); p > 0.05). Serum homocysteine concentration was significantly higher in the TT genotype with respect to CC and CT genotypes in both the control group (p < 0.01) and patient group (p < 0.01). Systolic and diastolic blood pressures in subjects with different MTHFR genotypes did not differ significantly. In conclusion, MTHFR C677T mutation was significantly related to hyperhomocysteinemia. In spite of the clear effect of the MTHFR polymorphism on elevated homocysteine levels, we did not observe any associations among the MTHFR genotypes with a the risk of CAD in the Turkish population.     

Association of TLR and TREM-1 gene polymorphisms with risk of coronary artery disease in a Russian population

Atherosclerosis, manifesting itself as acute coronary syndrome, stroke, and peripheral arterial diseases, is a chronic progressive inflammatory disease which is driven by responses of both innate and adaptive immunity. Toll-like receptors (TLRs) and Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) are important effectors of the innate immune system, and polymorphisms within genes encoding them may increase risk of occurrence of various pathologies including cardiovascular disorders. Thus, we carried out a genetic association study on the sample of 702 consecutive Caucasian (Russian) patients with coronary artery disease (CAD) and 300 age-, sex-, and ethnicity-matched healthy controls. We revealed that the C/C genotype of the TLR1 rs5743551 polymorphism was significantly associated with a reduced risk of CAD according to the recessive model (OR = 0.41, 95% CI = 0.20–0.84, P = 0.017, adjusted by age and gender). Concerning TREM-1 gene polymorphisms, we found that A/A genotype of the rs2234237 polymorphism, the G/G genotype of the rs6910730 polymorphism, the C/C genotype of the rs9471535 polymorphism, and the T/T genotype of the rs4711668 polymorphism were significantly associated with elevated CAD risk according to the recessive model (OR = 5.52, 95% CI = 1.17–25.98, P = 0.011; OR = 4.28, 95% CI = 1.09–16.81, P = 0.021; OR = 5.55, 95% CI = 1.18–26.09, P = 0.011, and OR = 1.66, 95% CI = 1.10–2.52, P = 0.014, respectively, adjusted by age and gender). Conversely, the G allele of the rs1817537 polymorphism, the T allele of the rs2234246 polymorphism, and the T allele of the rs3804277 polymorphism significantly correlated with similarly decreased risk of CAD according to the dominant model (OR = 0.57, 95% CI = 0.40–0.81, P = 0.0013; OR = 0.59, 95% CI = 0.42–0.84, P = 0.003, and OR = 0.58, 95% CI = 0.41–0.81, P = 0.0014, respectively, adjusted by age and gender). We conclude that certain TLR and TREM-1 gene polymorphisms may be associated with CAD in Russian population; however, their significance as predictive and pathogenic markers of CAD should be interpreted with caution in other populations.     

Association of fibrinogen and plasmin inhibitor,but not coagulation factor XIII gene polymorphisms with coronary artery disease

BackgroundIn the final phase of clot formation, fibrinogen constitutes frame, whereas factor XIII (FXIII) active form is responsible for the covalent cross-linking of fibrin fibres and plasmin inhibitor (PI), thus contributing to clot stability. It could be expected that any change of coagulation factors'' structure affects the clot formation and modulates the atherothrombotic risk. The aim was to determine the frequency of four single nucleotide polymorphisms: (i) A > G in codon 312 of the fibrinogen α-chain gene (rs6050, Thr312AlaFGA), (ii) C > T at position 10034 of the 3 - untranslated region in the fibrinogen γ-chain gene (rs2066865, 10034C > T FGG), (iii) C > T in codon 564 of the FXIII-A subunit gene (rs5982, Pro564LeuFXIII-A), and (iv) C > T in codon 6 of the plasmin inhibitor gene (rs2070863, Arg6TrpPI) in Croatian patients and their association with coronary artery disease (CAD).MethodsWe performed the unrelated case-control association study on the consecutive sample of patients 18 years old, who had undergone coronary angiography for investigation of chest pain and suspected CAD. The cases were patients with confirmed CAD (N=201), and the controls were the subjects with no CAD (N=119). Samples were genotyped using PCR-RFLP analysis.ResultsObserved frequencies of the rare alleles of Thr312Ala FGA, 10034C > T FGG, Leu564Pro FXIII-A and Arg6Trp PI polymorphisms were 21%, 17%, 14%, 20%, respectively. Patients with 10034C > T FGG CC genotype had 3.5 times (95% CI 1.02-12.03) higher adjusted odds for CAD than patients with 10034C > T FGG TT genotype. Patients with Arg6Trp PI CC genotype had 3.86 times (95% CI 1.23-12.12) higher odds for CAD than patients with Arg6Trp PI TT genotype. It seems that those genotype-related higher odds are also male-gender related. No difference was observed regarding any other investigated polymorphism.ConclusionsOur finding suggests that 10034C > T FGG and Arg6Trp PI are associated with CAD.     

CDKN2B-AS1 gene rs4977574 A/G polymorphism and coronary heart disease: A meta-analysis of 40,979 subjects

It has been implied that there is a possible relationship between cyclin-dependent protein kinase inhibitors antisense RNA 1 (CDKN2B-AS1) gene rs4977574 A/G polymorphism and coronary heart disease (CHD) susceptibility. However, as the research results are discrepant, no distinct consensus on this issue has been reached so far. In order to further elaborate the latent association of the CDKN2B-AS1 gene rs4977574 A/G polymorphism and CHD, this present meta-analysis was conducted. There were 40,979 subjects of 17 individual studies in the present meta-analysis. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to determine the association strength. Considering the significant heterogeneity among the individual studies, the random-effect models were used. In the current meta-analysis, a significant association between CDKN2B-AS1 gene rs4977574 A/G polymorphism and CHD was found under allelic (OR: 1.18, 95% CI: 1.08–1.29, p = 4.83×10⁻⁴), recessive (OR: 1.36, 95% CI: 1.11–1.67, p = 0.003), dominant (OR: 0.71, 95% CI: 0.58–0.86, p = 6.26×10⁻⁴), heterozygous (OR:1.210, 95% CI: 1.076–1.360, p = 0.001), homozygous (OR: 1.394, 95% CI: 1.163–1.671, p = 3.31×10⁻⁴) and additive (OR: 1.180, 95% CI: 1.075–1.295, p = 4.83×10⁻⁴) genetic models. A more significant association between them was found in the Asian population than that in the whole population under these genetic models (p < 0.05). However, no significant association between them was found in the Caucasian population (p > 0.05). CDKN2B-AS1 gene rs4977574 A/G polymorphism was associated with CHD susceptibility, especially in the Asian population. G allele of CDKN2B-AS1 gene rs4977574 A/G polymorphism is the risk allele for CHD.     

SOD3 R231G polymorphism associated with coronary artery disease and myocardial infarction. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study

This study examined the superoxide dismutase 3 (SOD3) R231G polymorphism in relation to the severity of coronary artery disease (CAD) and the risk of myocardial infarction (MI) in 3211 individuals; 94.4% of study participants were homozygous for SOD3 231RR and 5.5% were heterozygous for SOD3 231RG. The odds ratios of the RG and GG genotype (adjusted for age, gender and for conventional cardiovascular risk factors) were 2.02 (95% CI, 1.23–3.33, p=0.005) for the highest vs the lowest Friesinger coronary score and 1.40 (95% CI, 1.02–1.92, p=0.037) for MI, respectively. Further the SOD3 RG and GG genotype was associated with lower alpha-tocopherol levels than the wild type SOD3 RR genotype. It is concluded that the SOD3 231RG and GG genotype is associated with lower alpha-tocopherol levels and the severity of CAD and the risk of MI.     

NO Level and Endothelial NO Synthase Gene Polymorphism （Glu298Asp） in the Patients with Coronary Artery Disease from the Turkish Population

A healthy endothelium plays a core role in cardiovascu-lar control [1]. In the endothelial cell, nitric oxide (NO) issynthesized by the endothelial nitric oxide synthase (eNOS)encoded by a 26-exon gene (NOS 3) located on chromo-some 7 [2]. Besides its regulatory functions on vasomotortone and blood flow, endothelial NO is known to inhibitthe platelet activation and modulate migration and growthof the vascular smooth muscle [3]. Indirect evidence sug-gests that alterations of the NO pathwa…