Mannose-Binding Lectin Haplotypes and Infection Risk

甘露糖结合凝集素单倍型和感染风险

• 批准号: 6793437
• 负责人: JOHN E LANDERS
• 金额: $ 12.26万
• 依托单位: POLYGENYX, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2004-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6793437
• 关键词: DNA; complement; diagnostic tests; disease /disorder proneness /risk; gene expression; genetic susceptibility; genotype; high throughput technology; human genetic material tag; immune response; infection; lectin; mannose; oligonucleotides; opsonin; polymerase chain reaction; selectins; single nucleotide polymorphism; technology /technique development

DESCRIPTION (provided by applicant): Mannose-binding lectin (MBL) plays an important role in the innate immune response via its ability to recognize sugar moieties on the surfaces of a great variety of pathogens. MBL binding leads to destruction by opsonization and/or activation of the complement pathway in an antibody-independent manner. Thus, MBL deficiency has been associated with numerous immune-related diseases including rheumatoid arthritis, systemic lupus erythematosus, and severe infections in children and immunocompromised adults. In addition, the progression of several diseases, including cystic fibrosis, hepatitis BIC and HIV, are also associated with MBL expression. The transcription and functional activity of MBL depend upon polymorphisms within the gene and their phase or haplotypic configuration. Therefore, the ability to easily and inexpensively determine an individual's MBL haplotype would help establish a stronger link between MBL and disease susceptibility and progression, and aid in the development of a diagnostic test. This Phase I proposal applies PolyGenyx's novel molecular SNP haplotyping approach to developing a highthroughput assay for 12 polymorphisms within the MBL gene. Currently, no other method allows simple, reliable, accurate high-throughput haplotyping of SNP loci. Phase II studies are expected to associate an individual's MBL haplotype with risk of infection. Due to the wide variety of diseases influenced by MBL, the potential commercial applications for a haplotyping assay are diverse and economically attractive. For instance, the annual economic impact of rheumatoid arthritis is estimated at $15B in direct medical costs and $60B in indirect costs. For each disease, evaluating the patient's MBL status would be extremely beneficial. Patients with a haplotypic configuration predicting increased risk of disease/infection could undergo several steps to reduce this risk, improve their quality of life, and reduce the total economic impact to society.

描述（由申请人提供）：甘露糖结合凝集素（MBL）通过其在多种病原体表面上识别糖部分的能力在先天免疫反应中起着重要作用。 MBL结合以抗体无关的方式导致补体途径的破坏和/或激活。因此，MBL缺乏症与许多与免疫相关的疾病有关，包括类风湿关节炎，全身性红斑狼疮以及儿童和免疫功能低下的成年人的严重感染。此外，包括囊性纤维化，BIC和HIV在内的几种疾病的进展也与MBL表达有关。 MBL的转录和功能活性取决于基因内的多态性及其相或单倍型构型。因此，轻松，廉价地确定个人的MBL单倍型的能力将有助于建立MBL与疾病敏感性和进展之间的更强联系，并有助于开发诊断测试。该阶段I建议将多弹性的新型分子SNP单倍型方法应用于MBL基因内的12种多态性的高通量测定法。当前，没有其他方法允许SNP基因座的简单，可靠，准确的高通量单倍型。 II期研究有望将个人的MBL单倍型与感染风险相关联。 由于受MBL影响的各种疾病种类繁多，因此单倍分析测定的潜在商业应用多样性地具有吸引力。例如，类风湿关节炎的年度经济影响估计直接医疗费用为15B美元，间接费用为60B美元。对于每种疾病，评估患者的MBL状况将非常有益。具有单倍型配置的患者预测疾病/感染风险增加的患者可能会采取多个步骤，以降低这种风险，改善其生活质量并减少对社会的总经济影响。