Associação do Genótipo e Fenótipo da Paraoxonase-1 com Angiografia Positiva para Doença Arterial Coronariana / Association of Paraoxonase-1 Genotype and Phenotype with Angiogram Positive Coronary Artery Disease

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.

Serum level of gamma-glutamyl transferase as a biomarker for predicting stenosis severity in patients with coronary artery disease

Background Gamma glutamyl transferase (GGT) is associated with pathogenesis of various diseases such as coronary artery disease (CAD). GGT activity displays an essential role in the catabolism of glutathione which is reported as a major antioxidant. The aim of this study was to explore the association of GGT activity with obstruction severity of artery in 500 CAD patients. Results Our finding showed a significant association between serum GGT activity and CAD patients. In particular, the level of GGT in patients who had ≥50% obstruction was higher, compared to healthy and patients with less than 50% obstruction in their coronary arteries (the level of GGT in patients with at least one (1 SVD), two (2VD), three (3VD) coronary artery obstruction were 55.6 ± 9.7, 71.7 ± 12.7 and 84.7 ± 13.4, while these values in patients with negative angio or control group were 28 ± 10 and 17 ± 4.6). Furthermore, the activity of this marker was associated with increased the risk of CAD (Odd ratio of GGT in 3VD group: 2, 95%CI: 1.8–2.3), which was also related with HDL-C. Of note, the level of GGT was enhanced progressively with increasing the obstruction severity of arteries. Conclusion We demonstrate the prognostic value of serum level of GGT as a biomarker for predicting obstruction severity in patients with CAD.

Serum Chemerin and Cardiovascular Risk Factors in Diabetic Subjects without Established Vascular Disease.

Aims: The current study aims to investigate serum chemerin as a potential cardiovascular marker in diabetic patients without established vascular diseases. Study Design: Case-Control study. Place and Duration of Study: The outpatients clinic, King Abdulaziz University Hospital in Jeddah, Saudi Arabia, between January 2013 and June 2014. Methodology: Ninety consecutive diabetic patients and 90 age- and sex-matched controls were recruited from King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Demographic, anthropometric and biochemical variables were estimated. Results: Overall and central obesity were highly prevalent among both groups. Serum chemerin was correlated with glycated hemoglobin (r= -0.207, p<0.05) and with C reactive protein (CRP) (r= 0.171, p<0.05). Moreover, serum chemerin was correlated with prothrombin time (r = -0.278, p<0.05) in control subjects and with diastolic blood pressure (r = -0.233, p<0.05) in diabetic subjects. Conclusion: We concluded that only glycated hemoglobin was significantly and independently correlated with serum chemerin levels.

Age and Gender as Determinants of Learning Style among Medical Students.

Background: An awareness of learning styles may help teachers modify their teaching methods to improve the educational outcomes of their students. Aim: The aim of this study was to determine the learning styles of medical students during their basic science training at Mashhad University Medical School (MUMS). Methods: The VARK (Visual, aural, read/write and kinesthetic learning styles) questionnaire was used to gather information on learning styles in 245 medical students during their basic science training at MUMS in 2014. The questionnaire was previously assessed for its validity and reliability. Data were analyzed using SPSS software. Results: Overall, 245 students (115 male/130 female) with a mean age of 22.17±2.27 years completed the questionnaire. Of these students 91.84% preferred a single- modal learning style and 8.16% of students preferred a multi-modal learning style. Of the students with a preference for a single modal learning style, 20% (45 students) had a preference for visual, and 53.33% (100 students) for auditory learning styles respectively; 22.22% (50 students) of students were categorized as single read-write and 4.44% (10 students) were classified as having a kinesthetic learning style preference respectively. Among the multi-modal group, 25% (5 students) of students preferred a bimodal and 75% (15 students) preferred a quad-modal learning style. There was a significant association between learning styles with age and gender (P<0.05), but there was no significant association between the preferred learning styles with marital status or place of residence (P>0.05). Conclusions: The key finding of our study was that learning style is age and gender dependent. Different teaching methods may be appropriate for men and women.