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Bioavailable Vitamin D Redefines Vitamin D Deficiency

生物可利用维生素 D 重新定义维生素 D 缺乏症

基本信息

批准号：
8511620
负责人：
RAVI THADHANI
金额：
$ 36.44万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-17 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8511620
关键词：
Adult Affect African American Bioavailable Biological Biological Assay Biology Blood specimen Bone Density Bone Diseases Caucasians Caucasoid Race Clinical Clinical Trials Design Complex Consensus Data Diabetes Mellitus Diagnosis Disease Disease Outcome End stage renal failure Enrollment Exhibits Fracture Future General Population Genes Genetic Polymorphism Healthcare Hormones Human Individual Interdisciplinary Study Link Longevity Malignant Neoplasms Measures Minority Neighborhoods Osteoporosis Outcome Patients Physiological Population Population Heterogeneity Pregnant Women Prevalence Prophylactic treatment Protein Binding Public Health Race Reporting Research Resources Risk Supplementation Testing Therapeutic Variant Vitamin D Vitamin D Deficiency Vitamin D-Binding Protein Work base cardiovascular disorder risk cardiovascular infection clinical decision-making clinically relevant cohort cost healthy aging healthy volunteer high risk improved innovation novel prevent public health priorities racial difference young adult

项目摘要

DESCRIPTION (provided by applicant): Vitamin D deficiency has been associated with bone disease and a host of other major non-skeletal diseases including cardiovascular, infection, cancer and diabetes. Although supplementation may reduce risks, the definitions and cutoffs that establish clinically relevant vitamin D deficiency across racially diverse populations lack consensus. As a public health priority, it is critical to determine who needs to be treated to optimally affect disease outcomes. Blacks consistently have low 25-hydroxy vitamin D (25[OH] D) levels but paradoxically have higher bone mineral density (BMD) and lower osteoporosis risk than whites. Should blacks be treated with vitamin D to prevent osteoporosis? We propose to investigate a novel concept that vitamin D binding protein (VDBP), in the context of the "free hormone hypothesis," underlies the physiological mechanisms of this paradox. We recently reported in healthy young adults that VDBP levels: (1) directly correlate with total 25(OH)D levels; (2) inversely correlate with free- and bioavailable-25(OH)D; and, importantly, (3) vary with race. Preliminary data collected by our research team in patients with ESRD and in pregnant women are consistent with these observations. Others have shown that polymorphisms of the VDBP gene exhibit marked racial differences, suggesting that VDBP modulates vitamin D activity. It is therefore likely that all blacks do not have profound free and bioavailable vitamin D deficiency. We plan to determine the influence of circulating VDBP on bioavailable 25(OH) D by comparing stored blood samples from a large (n~2,200) population of black and white subjects enrolled in HANDLS (Healthy Aging in Neighborhoods of Diversity across the Life Span (available at http://handls.nih.gov) to test the following hypotheses: 1. Blacks have lower levels of VDBP and total 25(OH) D, but similar levels of free and bioavailable 25(OH) D as whites. 2. Free and bioavailable 25(OH)D levels are independently associated with BMD in blacks and whites, inversely and linearly associated with PTH levels, and these associations are stronger than those between total 25(OH)D and BMD. Our specific aims are to: (1) determine VDBP, total and bioavailable 25(OH)D, and PTH levels; and (2) test for associations between BMD, bioavailable 25(OH)D, and PTH compared to total 25(OH)D.

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