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.

Evaluation of serum cathepsin D concentrations in coronary artery disease

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.

Distribution and genotype frequency of the C1431T and pro12ala polymorphisms of the peroxisome proliferator activator receptor gamma gene in an Iranian population.

BACKGROUND: Peroxisome proliferator activator receptor gamma (PPARγ) is a nuclear transcription factor regulating multiple genes involved in cell growth, differentiation, carbohydrate and lipid metabolism and energy production. Several genetic variations in the PPARγ gene have been identified to be associated with diabetes, obesity, dyslipidemia, insulin resistance, metabolic syndrome and coronary artery disease. The present study was designed to explore the distribution of two common single nucleotide polymorphisms of the PPARγ gene (C1431T and Pro12Ala) in an Iranian population. MATERIALS AND METHODS: Genotype frequencies for these two polymorphisms were compared for 160 healthy Iranian individuals with reports from other populations. The Genotyping was performed using real‑time polymerase chain reaction. RESULTS: The genotype distribution of the C1431T PPARγ polymorphism was 0.869 for the CC genotype, 0.119 for the CT genotype and 0.013 for uncommon TT genotype. Allelic frequencies were 0.93 for C and 0.07 for T allele respectively. For the Pro12Ala polymorphism of PPARγ gene, genotypic distributions and allelic frequencies were, 0.813 for CC, 0.181 for CG and 0.06 for GG and 0.903 for C and 0.097 for G respectively. Allelic and genotypic frequencies for both polymorphisms of PPARγ gene were in Hardy‑Weinberg equilibrium. CONCLUSIONS: Iran is a country with an ethnically diverse population and a comparison of allelic and genotypic frequencies of PPARγ C1431T and Pro12Ala polymorphisms between our population and others showed significant differences.

Glucokinase gene promoter -30G>A polymorphism: a cross-sectional association study with obesity, diabetes Mellitus, hyperlipidemia, hypertension and metabolic syndrome in an Iranian hospital / Polimorfismo -30G

OBJECTIVE: A -30G>A single nucleotide polymorphism in the promoter region of the glucokinase gene has been previously associated with obesity, insulin resistance and diabetes. The present study aimed to evaluate the association of this polymorphism with obesity and its comorbidities in a population from Northeast Iran. METHODS: Five hundred and forty-two subjects aged 18 to 65 years were included in the study and divided into normal (BMI<25, n=220), overweight (2530, n=187) groups. All subjects were genotyped for the -30G>A polymorphism using the polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The genotypes and allele frequencies of the three groups did not differ significantly (p>0.05). When the study population was categorized according to diabetes mellitus, hyperlipidemia, hypertension and metabolic syndrome status, no significant difference in -30G>A genotypes and alleles was found between the subgroups with and without these disorders (p>0.05), apart from a significantly higher frequency of the G allele in the hyperlipidemic vs. non-hyperlipidemic subgroup (p<0.05). CONCLUSION: The findings of the present study do not support an association between the -30G>A polymorphism and high body mass index in the Iranian population.

OBJETIVO: O polimorfismo de nucleotídeo único -30G>A, na região promotora do gene da glucoquinase, já foi associado à obesidade, resistência insulínica e diabete. O objetivo deste estudo foi avaliar a associação deste polimorfismo com a obesidade e suas comorbidades em uma população do nordeste iraniano. MÉTODOS: Quinhentos e quarenta e dois indivíduos com idades entre 18 e 65 anos foram divididos em três grupos: normal (BMI<25, n=220), sobrepeso (2530, n=187). Todos os indivíduos foram genotipados para o polimorfismo -30G>A através da técnica da reação em cadeia da polimerase - polimorfismo do comprimento do fragmento de restrição. RESULTADOS: As frequências dos genótipos e alelos dos 3 grupos não diferiram entre si (p>0,05). Quando a população de estudo foi categorizada de acordo com a presença de diabete, hiperlipidemia, hipertensão arterial e síndrome metabólica, os genótipos e alelos -30G>A dos subgrupos com e sem essas doenças não diferiram entre si (p>0,05), exceto por uma frequência maior do alelo G no grupo de hiperlipidêmicos quando comparados aos não hiperlipidêmicos (p<0,05). CONCLUSÃO: Os achados do presente estudo não confirmam uma associação entre o polimorfismo -30G>A e excesso de peso na população iraniana.

Serum zinc and copper concentrations and socioeconomic status in a large Persian cohort.

Background: We have previously reported that serum zinc (Zn) and copper (Cu) are affected by a number of factors. In the current investigation we have investigated the association between serum Zn and Cu concentrations and socio-economic factors in an Iranian population. Materials and methods: A Persian sample population (n = 2233; n = 1106 (49.5%) males and n = 1127 (50.5%) females) was recruited by cluster-stratified sampling. Individuals were aged 15-65 years, and included urban and rural residents of the Great Khorasan province, Iran. Anthropometric measurements, serum Zn and Cu analysis and socio-economic status were determined using standard protocols. Results: The mean serum Cu and Zn concentrations for the whole group were 14.7?3.3 ?mol /L (range 4.5-28.4 ?mol /L), and 11.7?1.9 ?mol/L (range 3.6-28.3 ?mol/L) respectively, and the mean serum Zn:Cu ratio for the group was 0.83?0.2. The highest mean copper concentrations were found in the age range 50-59 years (p < 0.01). The total population of urban residents had higher serum zinc (p <0.01) and lower serum copper concentrations (p <0.05) than rural residents. Poorly educated male subjects had significantly higher serum concentrations of copper than males in the other subgroups (p <0.001). Serum Cu and Zn:Cu ratio were associated with height and body mass indices (p <0.01). Conclusion: Low serum zinc and copper appears to be common in Persian individuals. Urbanization and also educational attainment may contribute to changes in serum levels of Cu and Zn. This is probably related to lifestyle habits.

Investigation of the effect of high dairy diet on body mass index and body fat in overweight and obese children.

Objective. To investigate whether an increase in dairy food consumption improves the changes in BMI and adiposity in children on an energy restricted diet. Methods. Overweight and obese children (n = 120, age: 12-18 Yr, BMI: 27-40 kg/m2) were randomized to receive a calorie restricted diet providing a 500 kcal/d deficit from total energy expenditure and two (n = 40), three (n = 40) or four (n = 40) servings of dairy products/day. Anthropometric measurements in addition to serum hs-CRP and lipid profile were measured at baseline and after 12 wk. Results. Among the 96 children who completed the study, significant reductions in overall BMI, BMI z-score, weight, total body fat percentage and total body fat mass were observed (p < 0.001) but these reductions were not significantly affected by increasing dairy intake (p > 0.05). Overall waist/hip ratio, Serum vitamin D and lipid profile did not change significantly (p > 0.05) apart from a significant increase in HDL-cholesterol (p < 0.001) which was independent of dairy intake (p > 0.05). Conclusion. Increased intake of dairy products does not lead to an augmented change in BMI, weight and body fat in overweight and obese children beyond what is achieved by calorie restriction.