7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      C1019T Polymorphism in the Connexin 37 Gene and Myocardial Infarction Risk in Premature Coronary Artery Disease

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: The C1019T polymorphism of the connexin-37 (GJA4) gene is a single-nucleotide polymorphisms involved in atherosclerotic plaque rupture and atherosclerosis predisposition. We examined the association between the C1019T polymorphism of the GJA4 gene and the occurrence of myocardial infarction (MI) in patients with premature coronary artery disease (CAD).

          Methods: Our study recruited 1000 patients with the final diagnosis of premature CAD and classified them into 2 groups: with a history of MI (n = 461) and without it (n = 539). The polymorphism variants were determined via the PCR–RFLP, and then genotyping was conducted through the high-resolution melting method. From a total of 1000 patients, 554 patients, who had been previously followed-up with a median follow-up time of 45.74 months vis-à-vis long-term major adverse cardiac events, were enrolled in this retrospective cohort phase.

          Results: The frequencies of the wild, heterozygous, and mutant genotypes of the C1019T polymorphism were 54.0%, 40.6%, and 5.4% in the MI group and 49.2%, 43.2%, and 7.6% in the non-MI group (p value = 0.187). After adjustment for the baseline covariates, no difference was found between the MI and non-MI groups apropos the frequency of the heterozygous genotype (p value = 0.625) and the mutant genotype (p value = 0.452). Regarding the level of human connexin-37, the serum level of this marker was not different between the MI and non-MI groups.

          Conclusion: The C1019T polymorphism of the GJA4 gene may not be useful for predicting the occurrence of MI in patients with premature CAD. The presence of this polymorphism in such patients may also have a low value for predicting long-term CAD complications.

          Related collections

          Most cited references20

          • Record: found
          • Abstract: found
          • Article: not found

          Connexin37 protects against atherosclerosis by regulating monocyte adhesion.

          A genetic polymorphism in the human gene encoding connexin37 (CX37, encoded by GJA4, also known as CX37) has been reported as a potential prognostic marker for atherosclerosis. The expression of this gap-junction protein is altered in mouse and human atherosclerotic lesions: it disappears from the endothelium of advanced plaques but is detected in macrophages recruited to the lesions. The role of CX37 in atherogenesis, however, remains unknown. Here we have investigated the effect of deleting the mouse connexin37 (Cx37) gene (Gja4, also known as Cx37) on atherosclerosis in apolipoprotein E-deficient (Apoe(-/-)) mice, an animal model of this disease. We find that Gja4(-/-)Apoe(-/-) mice develop more aortic lesions than Gja4(+/+)Apoe(-/-) mice that express Cx37. Using in vivo adoptive transfer, we show that monocyte and macrophage recruitment is enhanced by eliminating expression of Cx37 in these leukocytes but not by eliminating its expression in the endothelium. We further show that Cx37 hemichannel activity in primary monocytes, macrophages and a macrophage cell line (H36.12j) inhibits leukocyte adhesion. This antiadhesive effect is mediated by release of ATP into the extracellular space. Thus, Cx37 hemichannels may control initiation of the development of atherosclerotic plaques by regulating monocyte adhesion. H36.12j macrophages expressing either of the two CX37 proteins encoded by a polymorphism in the human GJA4 gene show differential ATP-dependent adhesion. These results provide a potential mechanism by which a polymorphism in CX37 protects against atherosclerosis.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Familial occurrence of coronary heart disease: effect of age at diagnosis.

            The occurrence of coronary heart disease and its main risk factors were assessed among the first degree relatives of 309 men from South and East Finland, including 203 men with fatal or nonfatal myocardial infarction and 106 healthy reference men under age 56 years. The younger the patient at the diagnosis of a first myocardial infarction, the more common was coronary heart disease in his parents and siblings. The risk of having coronary heart disease by age 55 was, respectively, 11.4, 8.3 and 1.3 times greater in the South and 6.7, 3.6 and 1.8 times greater in the East for the brothers of patients than for the brothers of reference subjects depending on whether the diagnosis of myocardial infarction in the patient had first been established before the age of 46 years of age 46 to 50 years or at age 51 to 55 years. Hypertension and hyperlipidemia, but none of the other risk factors studied, were most common among the relatives of the youngest patients and diminished in frequency with advancing age of the patient. Most of the strong familial component in coronary heart disease of early onset thus appears to be mediated by familial hyperlipidemias and hypertension. It is suggested that the risk of premature coronary heart disease in the persons at highest risk could be largely eliminated if information about family history were used to identify such persons at an early stage and if they were treated properly for their correctable risk factors.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors.

              The aim of the study was to identify genes that confer susceptibility to coronary artery disease (CAD) in low- or high-risk men or women separately and thereby to assess the genetic risk of CAD in such individuals. The prevention of CAD would be facilitated by the identification of genes that confer susceptibility to this condition independently in low- or high-risk individuals, as defined by conventional risk factors. The study population comprised 1661 unrelated Japanese individuals, including 1011 patients with CAD and 650 control subjects. Among all study subjects, 601 individuals (high-risk subjects) had hypertension, diabetes mellitus, and hypercholesterolemia, and 1060 individuals (low-risk subjects) had none of these risk factors for CAD. The genotypes for 37 polymorphisms of 31 candidate genes were determined by a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis, with adjustment for age, body mass index, and the prevalence of smoking and hyperuricemia, revealed that the -219G-->T polymorphism of the apolipoprotein E gene in low-risk men, the -1171/5A-->6A polymorphism of the stromelysin-1 gene in low-risk women, the 1019C-->T polymorphism of the connexin 37 gene in high-risk men, and the 3932T-->C polymorphism of the apolipoprotein E gene in high-risk women were significantly associated with CAD. A stepwise forward selection procedure revealed that the effects of these polymorphisms on CAD were statistically independent of age or conventional risk factors. Genotyping of these polymorphisms may prove informative for assessment of the genetic risk of CAD in low- or high-risk men or women.
                Bookmark

                Author and article information

                Journal
                J Tehran Heart Cent
                J Tehran Heart Cent
                JTHC
                The Journal of Tehran University Heart Center
                Tehran University of Medical Sciences, 2006- (Tehran, Iran )
                1735-5370
                2008-2371
                April 2017
                : 12
                : 2
                : 72-81
                Affiliations
                [1 ] Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
                [2 ] Department of Human Genetics, Tarbiat Modarres University, Tehran, Iran.
                Author notes
                [* ]Corresponding Author: Mohammad Ali Boroumand, Professor of Pathology, Pathology Department, Tehran Heart Center, North Kargar Street, Tehran, Iran. 1411713138. Tel: +98 21 88029256. Fax: +98 21 88029256 borumand@ 123456sina.tums.ac.ir
                Article
                JTHC-12-72
                5558058
                d433925d-f69d-400c-a5e7-1c5bdfbca5f7
                Copyright © 2015 Tehran Heart Center, Tehran University of Medical Sciences

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 September 2016
                : 17 December 2016
                Categories
                Original Article

                Cardiovascular Medicine
                genes,connexin 37,myocardial infarction,polymorphism, genetic
                Cardiovascular Medicine
                genes, connexin 37, myocardial infarction, polymorphism, genetic

                Comments

                Comment on this article