Vitamin K: Genetics of Vascular Calcification

冠状动脉和主动脉的血管钙化是冠心病和其他心血管疾病(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继续，它们的影响将越来越重要。相当大比例的冠心病风险是由可改变的冠状动脉危险因素引起的，如高血压、高脂血症和吸烟。这一知识已被用于实施成功的预防和治疗战略，以阻止20世纪后半叶发生的冠心病死亡率的增加。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修改因素可能会导致额外的有效干预措施，以减少 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，确定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和安全性相对较低。这项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饮食补充的反应的变异性。为此，我们将评估单核苷酸多态(SNPs)和某些候选基因[载脂蛋白E(APOE)、脂蛋白脂酶(LPL)、基质GLA蛋白(MGP)、维生素D受体(VDR)]单倍型与维生素K代谢相关指标、骨质疏松和血管钙化的基线水平之间的关系。此外，我们将通过以下方式分析基因 治疗交互作用，以确定被检查的基因对维生素补充反应的可变性的贡献。据我们所知，这是第一个研究基因变异对维生素K补充、年龄相关性骨丢失进展和血管钙化的影响的同类建议。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。 精神错乱。

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.