Iron Status: A Pathway Analysis in Multiple Ethnicities

描述（由申请人提供）：拟议的研究将确定参与全身性铁代谢途径的关键基因的单核苷酸多态性（SNP）和单倍型，确定铁缺乏症的潜在病例和对照，并研究铁缺乏症的存在与所选候选基因的单倍型之间的关联。缺铁是世界上最常见的疾病，估计有40亿至50亿人受影响。我们推测，常见的变异和/或单倍型的基因参与铁代谢将调节易感性或耐发展的铁缺乏症在多个种族群体。在HEIRS研究中，这是一项由NIH资助的研究，对101，168名参与者进行了铁状态和HFE基因常见突变的血清生化检测，大约50%的参与者来自非洲，亚洲，西班牙裔，美洲原住民或太平洋岛屿遗产，并确定了3，000多名缺铁个体。通过对选定的HEIRS参与者储存的血液样本进行分析，我们现在建议使用途径方法来测试铁缺乏症的存在与选定候选基因中的单倍型之间的关联。本研究的具体目的是：1.鉴定和确定HEIRS参与者中四个种族中涉及铁代谢途径的关键基因中常见单核苷酸多态性（SNP）和单倍型的等位基因频率。2.从通过HEIRS研究筛选的多种族参与者队列中定义铁缺乏症病例和对照组。我们预计筛查923例病例和1856例对照。3.研究铁缺乏症与候选基因单倍型的关系。将对来自病例和对照的DMA样本进行所选单倍型标记SNP的基因分型，并进行统计分析以确定最可能与铁缺乏相关的单倍型。公共卫生的好处是，这项研究将提供有关遗传因素导致缺铁的新信息。潜在的研究结果可用于识别有缺铁风险的个体，并制定创新的预防和治疗策略。

DESCRIPTION (provided by applicant): The proposed research will determine single nucleotide polymorphisms (SNPs) and haplotypes in key genes involved in systemic iron metabolism pathways, identify potential cases of iron deficiency and controls, and study the association between the presence of iron deficiency and haplotypes in the selected candidate genes. Iron deficiency is the most common disease in the world with an estimated 4-5 billion affected persons. We hypothesize that common variants and/or haplotypes in genes involved in iron metabolism will modulate the susceptibility or resistance to the development of iron deficiency in multiple ethnic groups. In the HEIRS Study, which is an NIH-funded study of 101,168 participants who were screened with serum biochemical tests of iron status and for common mutations of the HFE gene, approximately 50% of participants were of African, Asian, Hispanic, Native American, or Pacific Island heritage, and over 3,000 iron deficient individuals were identified. Through analysis of stored blood samples from selected HEIRS participants, we now propose to use a pathway approach to test for association between the presence of iron deficiency and haplotypes in selected candidate genes. The specific aims of the research are: 1. To identify and determine the allele frequency of common Single Nucleotide Polymorphisms (SNPs) and haplotypes in key genes involved in iron metabolism pathways in each of four ethnic groups represented in HEIRS participants. 2. To define a study group of cases of iron deficiency and controls from multi-ethnic cohort of participants screened through the HEIRS Study. We anticipate screening 923 cases and 1856 controls. 3. To study the association between the presence of iron deficiency and haplotypes in the selected candidate genes. DMA samples from the cases and controls will be genotyped for selected haplotype-tagging SNPs and statistical analyses will determine the most likely haplotypes associated with iron deficiency. The public health benefit is that the study will provide new information about causes of iron deficiency due to genetic factors. Potential study results could be used to identify individuals at risk for iron deficiency and to develop innovative prevention and treatment strategies.