GPCR Variants as Genetic Determinants of Obesity

GPCR 变异作为肥胖的遗传决定因素

基本信息

  • 批准号:
    7249490
  • 负责人:
  • 金额:
    $ 75.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-09-15 至 2010-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): More than 26 percent of the U.S. population has a body mass index (BMI) in excess of 30 and thus qualifies as obese. Although heritability is a well-established factor in the development of obesity, the genes underlying this tendency have been difficult to identify. One of the few monogenic forms of obesity identified to date results from mutations GPCR, MC4R. In light of this precedent and the need to define more common explanations underlying genetic susceptibility to obesity, it is of particular note that pharmacologic and/or genetic evidence has implicated more than twenty GPCRs as modulators of food intake, body weight and/or the hedonic (i.e., rewarding) response to feeding. The vast majority of these receptors have multiple known non-synonymous (i.e., changes in coding sequence) variants. By analyzing the prevalence, pharmacologic function, and co-existence of GPCR polymorphisms in the Look AHEAD population we will test our central hypothesis that a significant portion of obesity in the general population is linked with abnormal GPCR function. We will first define the MC4R variants (known and novel) in the Look AHEAD population by sequence and haplotype analysis. Aim 1 will provide insight into the role of this receptor in a large cohort of obese diabetic subjects as well as address the controversy surrounding the extent to which a known common variant (VI031) is protective against obesity. In addition, study of the MC4R will establish a baseline on which to explore the importance of other factors (e.g., GPCR polymorphisms) as genetic determinants of body weight. Furthermore, the analysis of the MC4R will enable other Look AHEAD investigators to take this variable into account as a potentially confounding factor in defining clinical susceptibilities. In Aim 2, we will genotype non-synonymous coding region polymorphisms and haplotype markers in a series of twenty orexigenic, anorexigenic and hedonic GPCRs postulated to have an etiologic role in the development of obesity. These receptor variants have been identified from the NCBI SNP database and from the literature. In parallel, corresponding mutant recombinant GPCRs will be expressed in heterologous cell lines and pharmacologically assessed. Polymorphic receptors will be classified as gain of function, loss of function, or wild type. The correlation between functional abnormalities and phenotypic parameters will be assessed within the study population. In Aim 3, combinations of anorexigenic, orexigenic and hedonic receptor variants will be assessed as potential synergistic or additive factors underlying the polygenic basis of obesity and/or other Look AHEAD study endpoints.
描述(由申请人提供):

项目成果

期刊论文数量(0)
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科研奖励数量(0)
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ALAN S KOPIN其他文献

ALAN S KOPIN的其他文献

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{{ truncateString('ALAN S KOPIN', 18)}}的其他基金

Lipidated Stable BAM8-22 Offers a Promising Therapeutic for Neuropathic Pain
脂化稳定 BAM8-22 为神经性疼痛提供了一种有前景的治疗方法
  • 批准号:
    9045171
  • 财政年份:
    2016
  • 资助金额:
    $ 75.88万
  • 项目类别:
Bursicon Receptor Antagonists: Templates for Developing Novel Insecticides
Bursicon 受体拮抗剂:开发新型杀虫剂的模板
  • 批准号:
    8441580
  • 财政年份:
    2012
  • 资助金额:
    $ 75.88万
  • 项目类别:
Bursicon Receptor Antagonists: Templates for Developing Novel Insecticides
Bursicon 受体拮抗剂:开发新型杀虫剂的模板
  • 批准号:
    8327959
  • 财政年份:
    2012
  • 资助金额:
    $ 75.88万
  • 项目类别:
Genetic Analysis of Feeding Behavior and Fat Deposition
摄食行为和脂肪沉积的遗传分析
  • 批准号:
    7037357
  • 财政年份:
    2006
  • 资助金额:
    $ 75.88万
  • 项目类别:
Genetic Analysis of Feeding Behavior and Fat Deposition
摄食行为和脂肪沉积的遗传分析
  • 批准号:
    7173715
  • 财政年份:
    2006
  • 资助金额:
    $ 75.88万
  • 项目类别:
Genetic Analysis of Feeding Behavior and Fat Deposition
摄食行为和脂肪沉积的遗传分析
  • 批准号:
    7564783
  • 财政年份:
    2006
  • 资助金额:
    $ 75.88万
  • 项目类别:
Genetic Analysis of Feeding Behavior and Fat Deposition
摄食行为和脂肪沉积的遗传分析
  • 批准号:
    7339280
  • 财政年份:
    2006
  • 资助金额:
    $ 75.88万
  • 项目类别:
GPCR Variants as Genetic Determinants of Obesity
GPCR 变异作为肥胖的遗传决定因素
  • 批准号:
    7651076
  • 财政年份:
    2005
  • 资助金额:
    $ 75.88万
  • 项目类别:
GPCR Variants as Genetic Determinants of Obesity
GPCR 变异作为肥胖的遗传决定因素
  • 批准号:
    7454234
  • 财政年份:
    2005
  • 资助金额:
    $ 75.88万
  • 项目类别:
Molecular Analysis of Dopamine 2 Like Receptor Function
多巴胺 2 样受体功能的分子分析
  • 批准号:
    6869255
  • 财政年份:
    2005
  • 资助金额:
    $ 75.88万
  • 项目类别:

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