Polymorphisms of the Human Matrix Gla Protein ( MGP ) Gene, Vascular Calcification, and Myocardial Infarctionстатья из журнала
Аннотация: Abstract —The matrix Gla protein (MGP) is an important inhibitor of vessel and cartilage calcification that is strongly expressed in human calcified, atherosclerotic plaques and could modulate plaque calcification and coronary heart disease risk. Using a genetic approach, we explored this possibility by identifying polymorphisms of the MGP gene and testing their possible association with myocardial infarction (MI) and plaque calcification. Eight polymorphisms were identified in the coding and 5′-flanking sequences of the MGP gene. All polymorphisms were investigated in 607 patients with MI and 667 control subjects recruited into the ECTIM Study (Etude Cas-Témoins de l’Infarctus du Myocarde) and in 717 healthy individuals with echographically assessed arterial calcification and atherosclerosis who were participating in the AXA Study. In the ECTIM Study, alleles and genotypes were distributed similarly in patients and controls in the whole study group; in only 1 subgroup of subjects defined as being at low risk for MI were the concordant A −7 and Ala 83 alleles more frequent in patients with MI than in controls ( P <0.003). In the AXA Study among subjects with femoral atherosclerosis, the same alleles were more common in the presence than the absence of plaque calcification ( P <0.025). The other MGP polymorphisms were not associated with any investigated clinical phenotype. Transient transfection experiments with allelic promoter-reporter gene constructs and DNA-protein interaction assays were carried out to assess possible in vitro functionality of the promoter variants detected at positions −814, −138, and −7 relative to the start of transcription. When compared with the −138 T allele, the minor −138 C allele consistently conferred a reduced promoter activity of −20% ( P <0.0001) in rat vascular smooth muscle cells and of −50% ( P <0.004) in a human fibroblast cell line, whereas the other polymorphisms, including −7, displayed no evidence of in vitro functionality. We conclude that the A −7 or Ala 83 alleles of the MGP gene may confer an increased risk of plaque calcification and MI; however, the observed relationships are weak or limited to subgroups of patients and therefore need confirmation.
Год издания: 2000
Авторы: Stefan‐Martin Herrmann, Carl Whatling, Eva Brand, Viviane Nicaud, Jérôme Gariépy, Alain Simon, Alun Evans, Jean-Bernard Ruidavets, Dominique Arveiler, Gérald Luc, Laurence Tiret, Adriano Henney, François Cambien
Издательство: Lippincott Williams & Wilkins
Источник: Arteriosclerosis Thrombosis and Vascular Biology
Ключевые слова: Vitamin K Research Studies, Parathyroid Disorders and Treatments, Coagulation, Bradykinin, Polyphosphates, and Angioedema
Другие ссылки: Arteriosclerosis Thrombosis and Vascular Biology (PDF)
Arteriosclerosis Thrombosis and Vascular Biology (HTML)
PubMed (HTML)
Arteriosclerosis Thrombosis and Vascular Biology (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 20
Выпуск: 11
Страницы: 2386–2393