Functions of Lactoferrin Polymorphisms in an Oral Infection

乳铁蛋白多态性在口腔感染中的功能

基本信息

批准号：
8709782
负责人：
Kabilan Velliyagounder
金额：
--
依托单位：
RBHS-SCHOOL OF DENTAL MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8709782
关键词：
Functions Lactoferrin Polymorphisms Oral Infection

项目摘要

DESCRIPTION (provided by applicant): Aggregatibacter actinomycetemcomitans (Aa) has been implicated as the causative agent of localized aggressive periodontitis (LAP), a severe form of periodontal disease that can lead to premature tooth loss in adolescents. This rapid form of periodontal disease affects more than 70,000 adolescents annually in the US alone. African-Americans have a 15-fold greater incidence of the disease than Caucasian-Americans making LAP a disproportionate burden on minorities and the poor. We recently have identified two new polymorphisms of the lactoferrin (Lf) gene that are involved in LAP. One polymorphic alteration occurs at the codon 11 (alanine/threonine) and the other is localized in the LPS binding region at codon 29 (arginine/lysine). Preliminary data suggests that genetic polymorphisms of Lf may play a significant role in determining an individual's susceptibility to the LAP. The research outlined in this revised proposal will test this hypothesis using a mouse model and focusing on the functional characterization of genetic polymorphisms of Lf. The specific aims of the research are to 1) Generate bigenic Lf-variants/Lf-knockout mice; 2) Determine the anti-bacterial and anti-inflammatory activities against Aa colonization and infection in bigenic Lf-variants/Lf-/- and Lf-/- mice. The results of the proposed research will contribute to our understanding of the functional role of Lf polymorphisms in LAP and provide new approaches to prevention of this disease based on functional differences in single nucleotide polymorphisms (SNPs) in the Lf gene.

描述（由申请人提供）：聚集的放线菌Cetemcitans（AA）被认为是局部侵袭性牙周炎（LAP）的病因，这是一种严重的牙周疾病形式，可能导致青少年的过早牙齿脱落。这种快速形式的牙周疾病仅在美国就会影响70,000多名青少年。非裔美国人的疾病发病率比白人裔美国人高出15倍，这使膝盖对少数群体和穷人负担不成比例。我们最近确定了乳铁蛋白（LF）基因的两个新的多态性，它们涉及膝盖。一种多态性改变发生在密码子11（丙氨酸/苏氨酸），另一个多态性改变位于密码子29（精氨酸/赖氨酸）的LPS结合区域中。初步数据表明，LF的遗传多态性可能在确定个体对膝盖的敏感性方面起重要作用。该修订的提案中概述的研究将使用小鼠模型检验该假设，并着重于LF遗传多态性的功能表征。该研究的具体目的是1）产生bigenic lf-variants/lf-knockout小鼠； 2）确定临后LF-Varianiants/lf - / - 和LF - / - 小鼠的抗细菌和抗炎活性。拟议研究的结果将有助于我们理解LF多态性在膝盖中的功能作用，并基于LF基因中单核苷酸多态性（SNP）的功能差异，为预防该疾病提供了新的方法。