Association of G-33A Polymorphism in the Thrombomodulin Gene with Myocardial Infarction in Koreans.

Park, Hyun-Young; Nabika, Toru; Jang, Yangsoo; Kwon, Hyuck Moon; Cho, Seung Yun; Masuda, Junichi

doi:10.1291/hypres.25.389

Cited by 23 publications

(31 citation statements)

References 26 publications

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“…The G33A polymorphism in thrombomodulin gene reduces promoter activity and was signiWcantly associated with MI (Ireland et al 1997;Park et al 2002), CAD (Li et al 2000) and carotid atherosclerosis (Li et al 2001). Conversely, in another study no association between the G33A polymorphism and CAD/MI was observed (Zhao et al 2005).…”

Section: Genes Associated With Arterial Thrombosismentioning

confidence: 94%

“…The 1G/ 2G polymorphism in the MMP-1 gene could inXuence risk of CAD (Ye et al 2003) and the MMP-1 2G/2G genotype in combination with stromelysin-1 6A/6A genotype signiWcantly increased the risk factor for carotid artery atherosclerosis (Ghilardi et al 2002). The MMP9 (Gelatinase B) C1562T polymorphism was also associated with CAD risk (Cho et al 2002;Ghilardi et al 2002;Zhang et al 1999). In a large study an association of composite C1562T/R279Q polymorphisms in MMP-9 gene with MI was observed.…”

Section: Genes Associated With Vascular Remodelingmentioning

confidence: 99%

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Molecular genetics of atherosclerosis

2009

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Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic polymorphisms significantly influence susceptibility to atherosclerotic vascular diseases. A large number of candidate genes, genetic polymorphisms and susceptibility loci associated with atherosclerotic diseases have been identified in recent years and their number is rapidly increasing. In this review we focus on some of the major candidate genes and genetic polymorphisms associated with human atherosclerotic vascular diseases.

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Section: Genes Associated With Arterial Thrombosismentioning

confidence: 94%

Section: Genes Associated With Vascular Remodelingmentioning

confidence: 99%

Molecular genetics of atherosclerosis

2009

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“…Individuals, especially young patients in Taiwan, with the G-33A polymorphism carry a higher risk of acute myocardial infarction (22), and the risk is further increased by smoking (6). Similarly, in Koreans, the G-33A polymorphism of the TM gene may be a genetic risk factor for myocardial infarction, as a result of abnormal promoter activity (23). In the Japanese population, those with a haplotype consisting of A2729C and C1418T of the TM gene have a higher risk of developing deep vein thrombosis (24).…”

Section: Discussionmentioning

confidence: 99%

Thrombomodulin Gene Polymorphism (C1418T) is Associated with the Development of Coronary Allograft Vasculopathy

et al. 2013

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The first two authors contributed equal to this work Thrombomodulin (TM) is the endothelial cell membrane-bound anticoagulant protein cofactor in the thrombin-mediated activation of protein C. Previous evidence has been reported regarding the association between TM polymorphisms and coronary artery disease. Allograft rejection-mediated vasculopathy is the main cause of death at more than one year after heart transplantation. However, whether TM polymorphism is associated with allograft rejection is still unclear. We analyzed the TM gene polymorphism C1418T using allele-specific primers in a PCR assay in 60 patients who underwent heart transplantation. The retrospective clinical data were collected and tested for any correlations with the TM gene polymorphism. We separated the patients into 2 groups according to their TM genotype (group 1: CC genotype; group 2: cre-TT genotype). Additionally, we generated expression constructs (TM fulllength-Cl418 and TM fulllength-TI418) and performed in vitro studies to explore the correlation between the TM C1418T polymorphism and the migration of smooth muscle progenitor cells and monocytes, which may be involved in the development of vasculopathy. The results showed that the levels of CD68, C4d, PAS, and Masson staining in the CT/TT genotype group increased at year 1 and continued to increase throughout the 3 years. These levels were higher than those observed in the CC genotype group. The ISHLT-WF2004 grade ofthe CT/TT genotype group was significantly different from that of the CC genotype group at the same time point post-transplantation. The coronary allograft vasculopathy (CAY) score was significantly different between the CC and CT/TT genotype groups at 1 and 3 years post-transplantation. Our in vitro studies demonstrate that both smooth muscle progenitor cells and monocytic THP-l cells with either the CT-1418 or the TT-1418 TM genotype have higher migratory abilities than cells with the CC-1418 genotype. Our results support a significant association between the TM C1418T polymorphism and the development of CAY after heart transplantation in the short-to medium-term.

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“…Polymorphisms in the promoter region of the TM gene were more common in patients diagnosed with MI than in matched controls. 146 The −33A allele has been associated with an increased risk of AMI and carotid atherosclerosis, [147][148][149] however, not consistently. 150 In the SMILE, the 25Thr allele was associated with MI, especially in young men and in the presence of additional risk factors (such as smoking and the presence of a metabolic risk factor: obesity, hypertension, or hypercholesterolemia).…”

Section: Protein C Pathwaymentioning

confidence: 99%