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Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene and increased risk for myocardial infarction in patients with premature coronary artery disease.

ABSTRACT: BACKGROUND:A number of matrix metalloproteinase (MMP) gene polymorphisms has been identified which may be probably related to premature myocardial infarction (MI). OBJECTIVE:We assessed the relationship between the two polymorphisms of the MMP9 gene including R279Q and C1562T and occurrence of premature MI. METHODS:The study has two phases including a case-control study as the first phase and cohort study as the second phase. Initially, 1000 patients with premature coronary artery disease were classified into MI and non-MI groups. Genotyping of the polymorphism was conducted by PCRRFLP and high-resolution melting techniques. Given the two conditions of patients residing in Tehran and faced with their first episode of MI, 640 of 1000 study samples previously followed up with a median follow-up time of 45.74 months were assessed in a retrospective cohort phase regarding long-term major adverse cardiac events (MACE). RESULTS:The prevalence of wild, heterozygous, and mutant genotypes of R279Q polymorphism in MI group was 14.5%, 57.3%, and 28.2% and in non-MI group was 36.9%, 38.4%, and 24.7%, respectively, with a considerable difference (P<.001). There was a significant difference in the prevalence of wild, heterozygous, and mutant genotypes of C1562T polymorphisms in MI group (12.4%, 41.2%, and 46.4%, respectively) and in non-MI group (46.8%, 38.6%, and 14.7%, respectively; P<.001). No difference was found in total MACE-free survival rate between genotypes of R279Q and C1562T polymorphisms. CONCLUSION:C1562T and R279Q polymorphisms are associated with the susceptibility to premature MI, but cannot predict long-term cardiac events in these patients.

SUBMITTER: Sheikhvatan M

PROVIDER: S-EPMC6817094 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene and increased risk for myocardial infarction in patients with premature coronary artery disease.

Sheikhvatan Mehrdad M Boroumand Mohammad Ali MA Behmanesh Mehrdad M Ziaee Shayan S

Journal of clinical laboratory analysis 20170428 1

<h4>Background</h4>A number of matrix metalloproteinase (MMP) gene polymorphisms has been identified which may be probably related to premature myocardial infarction (MI).<h4>Objective</h4>We assessed the relationship between the two polymorphisms of the MMP9 gene including R279Q and C1562T and occurrence of premature MI.<h4>Methods</h4>The study has two phases including a case-control study as the first phase and cohort study as the second phase. Initially, 1000 patients with premature coronary ...[more]

PMID: 28453874

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Project description:ObjectivesIdentification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with perioperative MI in patients undergoing coronary artery bypass grafting using genome-wide association methodology.Setting107 secondary and tertiary cardiac surgery centres across the USA.ParticipantsWe conducted a stage I genome-wide association study (GWAS) in 1433 ethnically diverse patients of both genders (112 cases/1321 controls) from the Genetics of Myocardial Adverse Outcomes and Graft Failure (GeneMAGIC) study, and a stage II analysis in an expanded population of 2055 patients (225 cases/1830 controls) combined from the GeneMAGIC and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) studies. Patients undergoing primary non-emergent coronary bypass grafting were included.Primary and secondary outcome measuresThe primary outcome variable was perioperative MI, defined as creatine kinase MB isoenzyme (CK-MB) values ≥10× upper limit of normal during the first postoperative day, and not attributable to preoperative MI. Secondary outcomes included postoperative CK-MB as a quantitative trait, or a dichotomised phenotype based on extreme quartiles of the CK-MB distribution.ResultsFollowing quality control and adjustment for clinical covariates, we identified 521 single nucleotide polymorphisms in the stage I GWAS analysis. Among these, 8 common variants in 3 genes or intergenic regions met p<10(-5) in stage II. A secondary analysis using CK-MB as a quantitative trait (minimum p=1.26×10(-3) for rs609418), or a dichotomised phenotype based on extreme CK-MB values (minimum p=7.72×10(-6) for rs4834703) supported these findings. Pathway analysis revealed that genes harbouring top-scoring variants cluster in pathways of biological relevance to extracellular matrix remodelling, endoplasmic reticulum-to-Golgi transport and inflammation.ConclusionsUsing a two-stage GWAS and pathway analysis, we identified and prioritised several potential susceptibility loci for perioperative MI.

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Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene and increased risk for myocardial infarction in patients with premature coronary artery disease.

Publications

Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene and increased risk for myocardial infarction in patients with premature coronary artery disease.

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