Iron Status: A Pathway Analysis in Multiple Ethnicities

描述(申请人提供)：建议的研究将确定涉及全身铁代谢途径的关键基因的单核苷酸多态(SNPs)和单倍型，确定潜在的缺铁和对照病例，并研究缺铁与所选候选基因单倍型之间的关系。缺铁是世界上最常见的疾病，估计有40-50亿人受到影响。我们假设，参与铁代谢的基因的常见变异和/或单倍型将调节多个民族对缺铁的易感性或抵抗力。这项继承人研究是由美国国立卫生研究院资助的，共有101,168名参与者参加，他们接受了铁状态的血清生化测试和HFE基因的常见突变筛查，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，并发现了3000多名铁缺乏者。通过对选定继承人参与者的储存血液样本的分析，我们现在建议使用一种途径方法来测试选定候选基因中铁缺乏的存在与单倍型之间的关联。本研究的具体目的是：1.鉴定和测定铁代谢途径中常见的单核苷酸多态(SNPs)等位基因频率和铁代谢途径关键基因的单倍型。2.从通过继承人研究筛查的多民族队列参与者中确定缺铁病例和对照病例的研究组。我们预计筛查923例病例和1856名对照。3.研究铁缺乏与所选候选基因单倍型的关系。来自病例和对照的DNA样本将进行选定的单倍型标记SNPs的基因分型，统计分析将确定最有可能与缺铁相关的单倍型。对公众健康的好处是，这项研究将提供关于遗传因素引起的铁缺乏原因的新信息。潜在的研究结果可以用来确定有缺铁风险的个人，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.