Genetic and environmental influences on SLE and lupus-related autoimmunity

遗传和环境对系统性红斑狼疮和狼疮相关自身免疫的影响

基本信息

  • 批准号:
    8295201
  • 负责人:
  • 金额:
    $ 24.87万
  • 依托单位:
  • 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:
    2012-07-01 至 2017-06-30
  • 项目状态:
    已结题

项目摘要

Systemic lupus erythematosus (SLE) affects a significant number of young African American women. The prevalence and severity of SLE in African American women is increasing despite recent advances in diagnosis and treatment. The etiology of the aggressive disease phenotype in African Americans is unknown. Development of SLE is believed to be due to a genetically susceptible individual being exposed to a triggering environmental factor(s). To what degree and how genetic/environmental interactions contribute to development and severity of SLE in African Americans is unclear. The prevalence of SLE in African Americans is in contradiction to the reported SLE prevalence in West Africa, where it is a rare disease. This prevalence difference led to the "gradient hypothesis" that environmental and genetic differences between West Africans and African Americans resulted in the increased prevalence of SLE in the United States. The prevalence gradient suggests that comparative studies of genetically related cohorts from the two continents may provide insight into the gene-environment interactions that result in the development of SLE and SLEr elated autoimmunity. The Sea Island Gullah population of South Carolina is unique in their genetic homogeneity and low levels of genetic admixture. They offer a unique opportunity to study genetic, environmental and epigenetic differences between themselves and individuals living in their ancestral home of Sierra Leone. Environmental exposures are clearly different in Sierra Leone and coastal South Carolina while genetics are similar. Based on prior studies by others and our collaborative group, we hypothesize that there are gene-environment interactions leading to the development SLE and that comparing the Gullah versus Sierra Leoneans will allow identification of key pathogenic factors in SLE. To test this hypothesis, we will pursue the following Specific Aims: Aim 1. Test the hypothesis that differences in certain environmental exposures between Sierra Leone and coastal South Carolina are associated with the presence of SLE and SLE-related autoimmunity. Aim 2. Test the hypothesis that certain environmental exposures induce epigenetic changes that differ between the Gullah patients and controls and Sierra Leone Africans, and that these differences correlate with the presence of SLE and SLE-related autoimmunity. Aim 3. Test the hypothesis that genetic factors influencing expression of nitric oxide and other reactive intermediate genes are involved in the development of SLE. Using two unique cohorts genetically and culturally linked in novel genetic/environmental studies will likely identify key factors associated with development of SLE in African Americans.
系统性红斑狼疮(SLE)影响了相当数量的年轻非洲裔美国妇女。尽管最近在诊断和治疗方面取得了进展,但非裔美国妇女SLE的患病率和严重程度仍在增加。非裔美国人侵袭性疾病表型的病因尚不清楚。SLE的发展被认为是由于遗传易感个体暴露于触发环境因素所致。遗传/环境相互作用在多大程度上以及如何促进非裔美国人SLE的发展和严重程度尚不清楚。SLE在非裔美国人中的患病率与西非报告的SLE患病率相矛盾,在西非SLE是一种罕见疾病。这种患病率差异导致了“梯度假说”,即西非人和非洲裔美国人之间的环境和遗传差异导致了美国SLE患病率的增加。患病率梯度表明,来自两大洲的遗传相关队列的比较研究可能会提供深入了解导致SLE和SLE相关自身免疫发展的基因-环境相互作用。南卡罗来纳州的海岛古拉种群在其遗传同质性和低水平的遗传混杂性方面是独特的。他们提供了一个独特的机会,研究他们自己和生活在塞拉利昂祖先家园的个人之间的遗传、环境和表观遗传差异。塞拉利昂和沿海南卡罗来纳州的环境暴露明显不同,而遗传学相似。根据其他人和我们的合作小组先前的研究,我们假设有基因-环境相互作用导致SLE的发展,比较Gullah与塞拉利昂人将允许识别SLE的关键致病因素。为了验证这个假设,我们将追求以下具体目标:目标1。检验塞拉利昂和南卡罗来纳州沿海地区某些环境暴露的差异与SLE和SLE相关自身免疫的存在相关的假设。目标二。检验以下假设:某些环境暴露诱导的表观遗传变化在Gullah患者和对照组以及塞拉利昂非洲人之间存在差异,并且这些差异与SLE和SLE相关自身免疫的存在相关。目标3。检验影响一氧化氮和其他反应性中间基因表达的遗传因素参与SLE发展的假设。在新的遗传/环境研究中使用两个独特的遗传和文化相关的队列可能会识别与非裔美国人SLE发展相关的关键因素。

项目成果

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DIANE L KAMEN其他文献

DIANE L KAMEN的其他文献

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{{ truncateString('DIANE L KAMEN', 18)}}的其他基金

Environmental Determinants of Lupus among African Americans
非裔美国人狼疮的环境决定因素
  • 批准号:
    9768878
  • 财政年份:
    2016
  • 资助金额:
    $ 24.87万
  • 项目类别:
Environmental Determinants of Lupus among African Americans
非裔美国人狼疮的环境决定因素
  • 批准号:
    9354400
  • 财政年份:
    2016
  • 资助金额:
    $ 24.87万
  • 项目类别:
Impact of Pathogenic and Protective Environmental Exposures on Autoimmune Disease
致病性和保护性环境暴露对自身免疫性疾病的影响
  • 批准号:
    8970378
  • 财政年份:
    2015
  • 资助金额:
    $ 24.87万
  • 项目类别:
Genetic and environmental influences on SLE and lupus-related autoimmunity
遗传和环境对系统性红斑狼疮和狼疮相关自身免疫的影响
  • 批准号:
    8494004
  • 财政年份:
    2013
  • 资助金额:
    $ 24.87万
  • 项目类别:
Environmental Determinants of Autoimmunity among African Americans in Coastal SC
南卡罗来纳州沿海非裔美国人自身免疫的环境决定因素
  • 批准号:
    8293172
  • 财政年份:
    2009
  • 资助金额:
    $ 24.87万
  • 项目类别:
Environmental Determinants of Autoimmunity among African Americans in Coastal SC
南卡罗来纳州沿海非裔美国人自身免疫的环境决定因素
  • 批准号:
    7799579
  • 财政年份:
    2009
  • 资助金额:
    $ 24.87万
  • 项目类别:
Environmental Determinants of Autoimmunity among African Americans in Coastal SC
南卡罗来纳州沿海非裔美国人自身免疫的环境决定因素
  • 批准号:
    8102165
  • 财政年份:
    2009
  • 资助金额:
    $ 24.87万
  • 项目类别:
Environmental Determinants of Autoimmunity among African Americans in Coastal SC
南卡罗来纳州沿海非裔美国人自身免疫的环境决定因素
  • 批准号:
    7934068
  • 财政年份:
    2009
  • 资助金额:
    $ 24.87万
  • 项目类别:
Environmental Determinants of Autoimmunity among African Americans in Coastal SC
南卡罗来纳州沿海非裔美国人自身免疫的环境决定因素
  • 批准号:
    8066118
  • 财政年份:
    2009
  • 资助金额:
    $ 24.87万
  • 项目类别:
SYSTEMIC LUPUS ERYTHEMATOSUS IN GULLAH HEALTH (SLEIGH)
GULLAH HEALTH 中的系统性红斑狼疮(雪橇)
  • 批准号:
    7719572
  • 财政年份:
    2008
  • 资助金额:
    $ 24.87万
  • 项目类别:

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