ABSTRACT
Resumo Fundamento Tem sido demonstrado que um aumento dos níveis séricos de PON1 é protetor contra vários distúrbios. Foi relatado que vários polimorfismos de nucleotídeo único (SNPs, single nucleotide polymorphisms ) do gene PON1 estão associados a níveis e atividade de proteínas enzimáticas séricas. Objetivos Investigar a associação de SNPs do PON1 e atividade da paraoxonase sérica com a doença arterial coronariana (DAC). Métodos Foram estudados 601 pacientes não relacionados submetidos à angiografia coronária, incluindo aqueles com estenose >50% (N=266) e aqueles com estenose <30% (N=335). Os SNPs rs662 e rs840560 do gene da paraoxonase foram determinados utilizando o método ARMS-PCR e o SNP rs705379 foi genotipado utilizando análise de PCR-RFLP. A atividade da paraoxonase sérica foi medida utilizando paraoxon como substrato. O valor de p<0,05 foi considerado significante. Resultados A atividade da paraoxonase sérica não foi significativamente diferente entre os grupos de estudo. Após ajuste para idade, sexo, hipertensão, diabetes mellitus e dislipidemia, o genótipo GG e o modelo codominante de rs662 foram positivamente associados a uma angiografia positiva (respectivamente, OR = 2,424, IC 95% [1,123-5,233], p <0,05, OR = 1,663, IC 95% [1,086-2,547]). A atividade da paraoxonase sérica foi significativamente maior no alelo G e variante GG do polimorfismo rs662, alelo A e variante AA de rs854560 e alelo C e variante CC de rs705379. A análise de haplótipos mostrou que o haplótipo ATC foi significativamente mais prevalente no grupo com angiografia negativa. A análise entre os grupos indicou que o alelo A de rs662 foi significativamente associado à menor atividade da paraoxonase no grupo com angiografia positiva (p=0,019). Conclusões A presença do alelo G do polimorfismo de nucleotídeo único rs662 está independentemente associada ao aumento do risco de DAC.
Abstract Background It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. Objective To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). Methods A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. Results Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). Conclusions The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.
ABSTRACT
Background Coronary artery disease (CAD) cannot be sufficiently explained by the presence of traditional risk factors. Cathepsin D has been proposed to serve as a surrogate marker of atherosclerosis but its alterations in CAD patients have not been studied. Objective To evaluate serum cathepsin D concentrations in relation to the presence and severity of CAD. Materials and methods A total of 104 subjects were recruited; 71 patients with suspected CAD and 33 healthy subjects. Thirty-four patients had >50% coronary stenosis of at least one artery (CAD+); the remaining 37 patients had <50% stenosis (CAD−) based on angiography. CAD+ patients were sub-divided into three sub-groups with single (SVD; n = 15), double (2VD; n = 9), and triple vessel (3VD; n = 10) disease. Serum soluble cathepsin D concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Results Serum cathepsin D concentrations were significantly higher in the CAD+ compared with healthy control (p = 0.016) but not CAD− group (p = 0.098). Within the CAD+ group, patients with 3VD had significantly higher serum cathepsin D concentrations compared with the SVD group (p = 0.025), and also compared with the CAD− (p = 0.011) and SVD (p = 0.001) groups. No significant associations were found between serum cathepsin D concentrations and potential confounders including age, sex, blood pressure, smoking history and dyslipidemia. Conclusion Serum cathepsin D concentrations may be associated with the presence of CAD.
ABSTRACT
Aims: The aim of this study is to compare major risk factors in Coronary Artery Disease patients with significant atherosclerotic lesions in both genders. Study Design: Cross-Sectional study. Place and Duration of Study: From Aug 2012 to Dec 2013, 299 consecutive patients who underwent angiography at the coronary angiography laboratory in Ghaem hospital were enrolled in this study. Methodology: Demographic data was collected by an interviewer based on a checklist. Moreover, a member of our research group examined patients for weight, height, and blood pressure. For each patient a blood sample was taken and angiography was done by an expert. Statistical analysis was performed by SPSS version 11.5, using descriptive statistics, one-way ANOVA, and non-parametric equivalent, Kruskal- Wallis. p<0.05 was considered as statistically significant. Results: Participants in this study were Iranian and 52.8% were female. The females were older than males (mean age 59±10.14 vs 58±12.4); and the majority of them were married and lived in urban areas. Among 169 patients that were recruited in the study, 95 (55.6%) had a positive history of hypertension (HTN), 77 (46.4%) hyperlipidemia, and 55 (32.5%) type 2 Diabetes Mellitus (T2DM). The observed differences in these parameters between two genders were significant (P<0.001, P=0.001 and P=0.001), respectively. Among the participants, 40 (46.4%) were smokers (at present or in the past). Conclusion: Our results show that the prevalence of HLP, HTN and T2DM among Iranian women who belong to the CAD patients’ population is more than men.