Aggressive Periodontitis and Formylpeptide Receptor SNPs

侵袭性牙周炎和甲酰肽受体 SNP

基本信息

批准号：
7267969
负责人：
JOHN D WALTERS
金额：
$ 18.44万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-15 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7267969
关键词：
AR gene Address Adrenergic Receptor Affinity African American Alleles American Amino Acid Sequence Bacteria Bacterial Infections Binding Caucasians Caucasoid Race Chemokine (C-C Motif) Receptor 5 Chemotaxis Clinical Clinical Research Code Data Defect Dental Care Disease Esthetics Exhibits FPR1 gene Foundations Frequencies Future Genes Genetic Polymorphism Genetic Transcription Goals Human Individual Infection Inherited Ligand Binding Link Listeria monocytogenes Methods Molecular Mus Patients Periodontitis Play Population Predisposition Promoter Regions Receptor Gene Relative (related person)Reporting Research Resistance Risk Role Single Nucleotide Polymorphism Surface Testing Therapeutic Intervention Tooth Loss Translations United States Variant Work bone chemokine receptor cost design neutrophil pathogen promoter receptor receptor expression

项目摘要

DESCRIPTION (provided by applicant): Formylpeptide receptors (FPR) play an important role in helping polymorphonuclear leukocytes (PMN) locate and neutralize bacterial infections. Defects in FPR expression and PMN chemotaxis are common in patients with aggressive periodontitis (AP), a disorder that produces severe, rapid periodontal destruction. AP is most prevalent in African-Americans and exhibits a familial aggregation. Our studies show that AP is associated with the silent single nucleotide polymorphism (SNP) c.348T>C in the gene that encodes FPR. In African-Americans, the 348T allele occurs at a higher frequency in individuals with AP than in healthy controls (P = 0.001). We hypothesize that 348T is linked to one or more SNPs in the FPR gene promoter, which could contribute to impaired FPR expression and increased risk of developing AP. An analogous linkage of silent coding SNPs with promoter SNPs exists in the p2-adrenergic receptor gene. This project will explore the relationship between FPR SNPs, FPR expression defects, chemotaxis defects and susceptibility to AP in African-Americans. In Specific Aim 1, an FPR gene fragment will be cloned and sequenced to characterize: a) the association of c.348T>C (and other individual and linked SNPs in the FPR coding region) with AP, and b) the association of c.348T>C with SNPs in the FPR promoter region. In Specific Aim 2, the relationship of c.348T>C to defects in PMN chemotaxis and FPR expression will be characterized. If these studies confirm our hypothesis, they will lay the foundation for studies that will explain at the molecular level why c.348T>C is associated with defective FPR expression and justify a larger clinical study to develop methods to detect individuals susceptible to AP. If a valid indicator of susceptibility were available, it would be prudent to test young African-Americans who are at increased risk of developing AP for the presence of pathogens. Targeted therapeutic intervention to eliminate pathogens prior to clinical expression of AP could mitigate periodontal destruction, minimize functional and esthetic problems related to tooth loss, and reduce the cost of dental care.

描述（由申请人提供）：甲基肽受体（FPR）在帮助多形核白细胞（PMN）定位并中和细菌感染方面起着重要作用。 FPR表达和PMN趋化性缺陷在侵袭性牙周炎（AP）的患者中很常见，这种疾病会导致严重，快速的牙周破坏。 AP在非裔美国人中最普遍，并且表现出家族性聚集。我们的研究表明，AP与编码FPR的基因中的无声单核苷酸多态性（SNP）C.348T> C有关。在非裔美国人中，348T等位基因在AP患者中的发生频率高于健康对照组（P = 0.001）。我们假设348T与FPR基因启动子中的一个或多个SNP相关，这可能有助于FPR表达受损并增加发生AP的风险。 P2-肾上腺素受体基因中存在无声编码SNP与启动子SNP的类似连接。该项目将探讨非裔美国人中FPR SNP，FPR表达缺陷，趋化性缺陷和对AP的易感性之间的关系。在特定的目标1中，将克隆FPR基因片段并测序以表征：a）C.348T> c（以及FPR编码区域中其他个体和链接的SNP）与AP的关联，b）C.348T> c的关联是FPR启动子区域中C.348T> c的关联。在特定的目标2中，将表征C.348T> C与PMN趋化和FPR表达中缺陷的关系。如果这些研究证实了我们的假设，他们将奠定研究的基础，以解释分子级别的基础，为什么C.348T> C与FPR表达有缺陷有关，并证明更大的临床研究是合理的，以开发用于检测患者AP敏感的个人的方法。如果有有效的易感性指标，那么测试年轻的非洲裔美国人的敏感性将是谨慎的，这些非裔美国人患有病原体的风险增加了AP的风险。有针对性的治疗干预措施在AP的临床表达前消除病原体可以减轻牙周破坏，最大程度地减少与牙齿脱落有关的功能和美学问题，并降低牙科护理的成本。