Vitamin K: Genetics of Vascular Calcification

维生素 K：血管钙化的遗传学

• 批准号: 6894687
• 负责人: Jose M. Ordovas
• 金额: $ 8万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-15 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6894687
• 关键词: apolipoprotein E; calcification; cardiovascular disorder; clinical research; clinical trial phase III; diet therapy; dietary supplements; gene mutation; human subject; lipoprotein lipase; nutrition of aging; nutrition related tag; osteoporosis; pathologic process; patient oriented research; single nucleotide polymorphism; vitamin D; vitamin D receptors; vitamin K; vitamin metabolism; vitamin therapy

Vascular calcification of the coronary arteries and aorta is a risk factor for coronary heart disease (CHD) and other cardiovascular diseases (CVD). In addition, vascular calcification has also been associated with osteoporosis. Both CVD and osteoporosis represent major age-associated health problems and their impact will increase in importance as the global aging of the population continues. A substantial proportion of CHD risk results from modifiable coronary risk factors, such as hypertension, hyperlipidemia, and cigarette smoking. This knowledge has been used to implement successful prevention and therapeutic strategies to stop the increase in CHD mortality that took place during the latter part of the 20th Century. Likewise, identification of those modifiable factors that contribute to an increase in vascular calcification and a reduction in bone mass in older populations could lead to additional effective interventions to reduce the burden not only for CHD but also for fractures in the general population. From the standpoint of prevention, the identification of dietary risk factors common to both diseases is particularly important, because the relatively low cost and safety of dietary therapy. The primary objectives of this study are to identify genetic components underlying vitamin K metabolism, osteoporosis, and vascular calcification and the variability in response to dietary supplementation in elderly men and women. For this purpose, we will evaluate associations between single nucleotide polymorphisms (SNPs) and haplotypes at certain candidate genes [apolipoprotein E (APOE), lipoprotein lipase (LPL), Matrix Gla Protein (MGP), Vitamin D Receptor (VDR)] and baseline levels of vitamin K metabolism related measures, osteoporosis, and vascular calcification in 450 elderly subjects participating in a NIH funded phase III clinical study. Moreover, we will analyze gene by treatment interactions in order to determine the contribution of the genes examined to the variability in response to vitamin supplementation. To the best of our knowledge, this is the first proposal of its kind to study the influence of genetic variation in response to vitamin K supplementation, progression of age-related bone loss and vascular calcification. This research should provide the basis for more comprehensive genetic studies aimed to provide better identification of risk and more precise therapeutic approaches for these age-related disorders.

冠状动脉和主动脉的血管钙化是冠心病（CHD）和其他心血管疾病（CVD）的危险因素。此外，血管钙化也与骨质疏松症有关。心血管疾病和骨质疏松症都是与年龄相关的主要健康问题，随着全球人口老龄化的持续，它们的影响将变得越来越重要。很大一部分冠心病风险是由可改变的冠状动脉危险因素引起的，例如高血压、高脂血症和吸烟。这些知识已被用来实施成功的预防和治疗策略，以阻止 20 世纪后半叶发生的冠心病死亡率增加。同样，识别那些导致老年人群血管钙化增加和骨量减少的可改变因素可能会导致采取额外的有效干预措施，以减少老年人群中血管钙化的增加和骨量的减少。 不仅是冠心病的负担，也是普通人群骨折的负担。从预防的角度来看，识别这两种疾病共有的饮食危险因素尤为重要，因为饮食治疗的成本相对较低且安全。本研究的主要目的是确定维生素 K 代谢、骨质疏松症和血管钙化的遗传成分，以及老年男性和女性对膳食补充剂反应的变异性。为此，我们将评估某些候选基因 [载脂蛋白 E (APOE)、脂蛋白脂肪酶 (LPL)、基质 Gla 蛋白 (MGP)、维生素 D 受体 (VDR)] 和基线的单核苷酸多态性 (SNP) 和单倍型之间的关联参与 NIH 资助的 III 期临床研究的 450 名老年受试者的维生素 K 代谢相关指标、骨质疏松症和血管钙化水平。此外，我们将通过以下方式分析基因： 治疗相互作用，以确定所检查的基因对维生素补充反应变异性的贡献。据我们所知，这是同类研究中第一个研究遗传变异对维生素 K 补充、年龄相关骨质流失和血管钙化进展的影响的提案。这项研究应该为更全面的遗传学研究提供基础，旨在为这些与年龄相关的患者提供更好的风险识别和更精确的治疗方法。 失调。