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，确定潜在的缺铁病例和对照，并研究所选候选基因中缺铁与单倍型之间的关系。缺铁是世界上最常见的疾病，估计有40亿至50亿人受到影响。我们假设，参与铁代谢的基因中的常见变异和/或单倍型将调节多个民族对铁缺乏发展的易感性或抗性。继承人研究是美国国立卫生研究院资助的一项研究，对101168名参与者进行了血清铁状态生化测试和常见的HFE基因突变筛查，大约50%的参与者是非洲人、亚洲人、西班牙人、美洲原住民或太平洋岛屿血统，并确定了3000多名缺铁个体。通过对选定的继承人参与者储存的血液样本的分析，我们现在建议使用途径方法来测试选定候选基因中缺铁和单倍型之间的关联。本研究的具体目的是：1。目的：鉴定和确定参与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. 从继承人研究中筛选的多种族参与者中确定缺铁病例和对照组的研究群体。我们预计筛查923例病例和1856例对照。3. 研究候选基因缺铁与单倍型的关系。来自病例和对照的DMA样本将对选定的单倍型标记snp进行基因分型，统计分析将确定与缺铁相关的最可能的单倍型。这项研究对公众健康的好处是，它将提供有关由遗传因素引起的缺铁原因的新信息。潜在的研究结果可用于确定有缺铁风险的个体，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.