Vitamin D, Race/Ethnicity, Genotype, and Multiple Sclerosis

维生素 D、种族/民族、基因型和多发性硬化症

基本信息

批准号：
8658861
负责人：
ANNETTE M LANGER-GOULD
金额：
$ 59.21万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8658861
关键词：
25-hydroxyvitamin D Accounting Address Affect African American Age Alleles Area California Cell Line Computerized Medical Record Diet Epidemiologic Studies Ethnic Origin Ethnic group Family Study Gender Genes Genetic Genetic Determinism Genetic Predisposition to Disease Genotype Goals HLA-DRB1 Health Maintenance Organizations Hispanics Human Herpesvirus 4 Incidence Individual Infection Intervention Lead Mediator of activation protein Modeling Multiple Sclerosis Newly Diagnosed Obesity Pathogenesis Policies Population Population Study Predisposition Prevention strategy Promoter Regions Race Recruitment Activity Research Resources Risk Risk Factors Role Sample Size Serum Skin Smoking Subgroup Sun Exposure Supplementation Testing Ultraviolet B Radiation United States Universities Vitamin D Vitamin D Deficiency Vitamin D Response Element Vitamin Deficiency Vitamins base dietary supplements gene environment interaction high risk improved member nervous system disorder population based prevent racial and ethnic residence

项目摘要

DESCRIPTION (provided by applicant): Hypovitaminosis D is an important emerging risk factor for multiple sclerosis (MS). Because vitamin D deficiency is endemic worldwide, vitamin D supplementation offers a potentially high-impact strategy to reduce MS incidence. However, the role of vitamin D in MS risk likely varies by race/ethnicity and genetic background. These important relationships are poorly understood, which prevents a rational approach to developing global vitamin D supplementation policies. We propose to determine whether hypovitaminosis D is a more important risk factor for multiple sclerosis (MS) in certain subgroups, in particular those with darker skin or those who are genetically predisposed either to MS or hypovitaminosis D. To test these hypotheses, we propose to recruit 1000 individuals with incident MS including 250 African Americans and 330 Hispanics and 1000 matched control subjects from the multi-ethnic population of Kaiser Permanente Southern California (KPSC) members. The specific aims of the project are: 1) to determine whether hypovitaminosis D is associated with an increased risk of MS in African Americans and Hispanics; 2) to determine whether hypovitaminosis D is associated with an increased risk of MS in individuals who are positive for the main MS susceptibility allele, HLA-DRB1*15 compared with those who are negative for this allele (gene-environment interaction); and 3) to examine whether genetic determinants of hypovitaminosis D increase the risk of MS. The results of this study have the potential to guide global vitamin D supplementation policies and other MS prevention strategies and will improve our understanding of MS pathogenesis. The aims of this study cannot be addressed with any of the existing MS study populations because they consist predominantly of whites and lack information on vitamin D and/or genotype. This will be the first population-based study to examine the effect of hypovitaminosis D in non-white individuals, test for a gene-environment interaction between the main MS susceptibility allele and vitamin D and the first study to identify high-risk subgroups based on these factors. The proposed research addresses a critical barrier in developing global vitamin D supplementation policies and targeted interventions to prevent MS.

描述（由申请人提供）：次生胺病D是多发性硬化症（MS）的重要新兴风险因素。由于维生素D缺乏症是全球流行的，因此补充维生素D提供了一种潜在的高影响力策略来降低MS的发生率。但是，维生素D在MS风险中的作用可能因种族/种族和遗传背景而异。这些重要的关系知之甚少，这阻止了制定全球维生素D补充政策的理性方法。我们建议确定某些亚组中多发性硬化症（MS）的不足危险因素，尤其是皮肤较暗的人，或者是遗传上对MS或遗传性易感性的危险因素。 Permanente南加州（KPSC）成员。该项目的具体目的是：1）确定非裔美国人和西班牙裔MS的风险增加是否与增加的MS风险有关； 2）确定dybovitaminiso D与主要MS易感性等位基因呈阳性的个体的MS风险增加有关，HLA-DRB1*15与该等位基因阴性的人（基因 - 环境相互作用）相比； 3）检查遗传性遗传决定因素是否会增加MS的风险。这项研究的结果有可能指导全球维生素D补充策略和其他MS预防策略，并将提高我们对MS发病机理的理解。这项研究的目的无法与任何现有的MS研究人群有关，因为它们主要由白人组成，并且缺乏有关维生素D和/或基因型的信息。这将是第一项基于人群的研究，以检查非白人病的效果在非白人个体中，测试主要MS易感性等位基因和维生素D之间的基因环境相互作用，以及基于这些因素鉴定高风险亚组的第一个研究。拟议的研究解决了制定全球维生素D补充政策和针对预防MS的靶向干预措施的关键障碍。