Effects of myeloperoxidase −463 G/A gene polymorphism and plasma levels on coronary artery disease

Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, 34280, Capa Istanbul, Turkey.
Molecular Biology Reports (Impact Factor: 1.96). 02/2011; 38(2):887-91. DOI: 10.1007/s11033-010-0181-4
Source: PubMed

ABSTRACT Myeloperoxidase is a lysosomal enzyme of polymorphonuclear leucocytes that contributes to inflammatory responses. In previous studies it was shown that MPO was synthesized in atherosclerotic lesions responsible of lipoprotein oxidations. We aimed to determine the MPO -463 G/A gene polymorphism distribution in Turkish population and evaluate the effects of it on myeloperoxidase levels. There were 100 myocardial infarct patients and 100 healthy control subjects in our study. MPO polymorphism was studied by using PCR-RFLP technique and MPO levels were measured by ELISA. It was shown that MPO levels were increasing in patients after myocardial infarct event but there were no effect of MPO -463 G/A polymorphism on MPO levels. It was also found that serum total cholesterol and LDL-cholesterol levels and smoking was contributing factors in increments of MPO enzymes. We observed that MPO levels were increased in CAD but there were no effect of MPO -463 G/A polymorphism on MPO levels.

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    ABSTRACT: Genetic polymorphism of human myeloperoxidase (MPO) -463G/A has been implicated to alter the risk of coronary artery disease (CAD), but the results are controversial. To improve the reliability of the conflicting results, we conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with the risk of CAD. Two investigators independently searched the MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR) and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk were calculated, and potential sources of heterogeneity and publication bias were explored. Statistical analysis was performed with the software program of Stata 9.0. 5 case-control studies were finally identified for analyses, involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A polymorphism has no significant association with overall CAD risk (G/G vs A/A: OR=0.595, 95%CI=0.298-1.188, P=0.141; G/G vs G/A+A/A: OR=0.886, 95%CI=0.779-1.008, P=0.066; G/G+G/A vs A/A: OR=0.611, 95%CI=0.334-1.119, P=0.111; OR=0.886, 95%CI=0.779-1.008, P=0.066; G vs A: OR=0.843, 95%CI=0.675-1.053, P=0.133). The heterogeneity test showed that there were significant differences between individual studies in additive, recessive and allelic genetic model (P=0.008, P=0.021, P=0.019, respectively), further analyses revealed that age and sex possibly account for the heterogeneity. Our meta-analysis demonstrated the evidence that there was no significant association between the MPO -463G/A polymorphism and the risk of CAD, larger and well-designed multicenter studies are needed to confirm our results.
    Clinical biochemistry 09/2013; 46(16-17). DOI:10.1016/j.clinbiochem.2013.09.002 · 2.23 Impact Factor
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    ABSTRACT: Abstract Context: Myeloperoxidase is a heme protein secreted by activated macrophages and generates intermediates that oxidize lipoproteins. Myeloperoxidase-463G/A is a functional polymorphism involved in regulation of myeloperoxidase expression. Objective: The aim of this study is to assess the relation of myeloperoxidase-463G/A polymorphism with metabolic syndrome and its component traits in Egyptian women from the Suez Canal area. Methods: The study includes 100 healthy female subjects and 100 metabolic syndrome patients. The component traits of metabolic syndrome are determined and the genotypes of the polymorphisms assessed using the PCR-RFLP technique. Results: There was no significant difference in the allele frequencies between the metabolic syndrome and control groups. However, the GA and AA genotypes were associated with lower total cholesterol, LDL-C, systolic and diastolic blood pressure in the patients. Conclusion: Myeloperoxidase-463G/A polymorphism is not associated with the incidence of metabolic syndrome.
    Archives of Physiology and Biochemistry 12/2014; DOI:10.3109/13813455.2014.988631
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    ABSTRACT: Increased systemic levels of myeloperoxidase (MPO) are associated with risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AA). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; p=4.89x10(-41)) and in 1690 AA subjects (rs505102; p =1.05 x 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare MPO coding sequence variants that were associated with serum MPO levels (rs28730837, p=5.21x10(-12); rs35897051, p=3.32x10(-8)). A GWAS for plasma MPO levels in 9260 European ancestry subjects identified a chromosome 17q22 region near MPO that was significantly associated (lead SNP rs6503905; p=2.94x10(-12)) but the CFH locus did not exhibit evidence of association with plasma MPO levels. Functional analyses revealed that rs800292 was associated with levels of complement proteins in serum. Variants at chromosome 17q22 also had pleiotropic cis effects on gene expression. In a case-control analysis of ∼80,000 subjects from CARDIoGRAM, none of the identified SNPs were associated with CAD. These results suggest that distinct genetic factors regulate serum and plasma MPO levels, which may have relevance for various acute and chronic inflammatory disorders. The clinical implications for CAD and a better understanding of the functional basis for the association of CFH and MPO variants with circulating MPO levels requires further study.
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