GENETIC CONTRIBUTIONS TO RISK FACTORS IN LJP

LJP 风险因素的遗传因素

基本信息

批准号：
2872155
负责人：
Thomas C Hart
金额：
$ 10.22万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-02-01 至 2000-01-31
项目状态：
已结题

项目摘要

Localized juvenile periodontitis (LJP) is a destructive type of periodontal disease that affects 2% of the African American population. LJP segregates within certain families, and individuals within these families are at increased risk for disease. Formal genetic studies conclude that LJP is transmitted as an autosomal dominant trait, indicating that a gene of major effect is important in LJP disease etiology. Several subforms of juvenile periodontitis are known to exist and each may be genetically different. Functional and morphological abnormalities have been reported in peripheral blood neutrophils of a significant percentage of LJP patients. Also a specific bacteria, Actinobacillus actinomycetemcomitans has shown a significant association with LJP. Certain genotypes of this bacteria may selectively exploit an inherent neutrophil defect in susceptible individuals. The central hypothesis of this study is that increased risk for LJP is due to an inherited neutrophil defect in susceptible individuals. The Aim of this study is to evaluate the role of several genetically controlled risk factors in LJP disease etiology. These include neutrophil receptors C5a, fMLP, and IL-8, as well as GP1 10, diacylglycerol kinase, annexin Ill and the vitamin D binding protein. Our study cohort will consist of 40 African American families (300 individuals) segregating for LJP. We will characterize these individuals for a number of disease presentation and host response variables including: clinical measures of periodontal tissue destruction, the presence of specific A. actinomycetemcomitans genotypes, and host immune response patterns including serum IgG response to A. actinomycetemcomitans and the density of neutrophil receptors (fMLP) and surface proteins (GP1 10) to assess heterogeneity in this African- American LJP population. We will then conduct linkage studies to evaluate the evidence for the role of specific neutrophil risk genes in the etiology of LjP in this population. Results will be assessed by calculation of pairwise logarithm of the odds (lod) scores to determine support for or against genetic linkage of each candidate marker to the LJP trait. Support for linkage will also be assessed using model free methods and will include formal analyses of heterogeneity. Systematic assessment of these candidate probes could ultimately provide positive risk markers with which to screen genetically susceptible populations at high risk for LJP, permitting early identification, diagnosis, and treatment.

局部青少年牙周炎（LJP）是一种破坏性类型影响非裔美国人人口的2％的牙周疾病。 LJP在某些家庭内部和个人内部分离家庭的疾病风险增加。正式的遗传研究得出结论，LJP是作为常染色体显性特征传播的，表明具有重大作用的基因在LJP疾病中很重要病因。已知少年牙周炎的几个亚事件存在每个都可能在遗传上不同。功能和形态学在A的外周血中性粒细胞中据报道异常 LJP患者的显着百分比。也是特定的细菌放线杆菌放肌ce骨表现出显着的关联与LJP。该细菌的某些基因型可以选择性地利用易感个体的固有中性粒细胞缺陷。中央这项研究的假设是，LJP的风险增加是由于易感个体的遗传性嗜中性粒细胞缺陷。这个目的研究是评估几种遗传控制风险的作用 LJP病病因的因素。这些包括中性粒细胞受体C5a， FMLP和IL-8，以及GP1 10，二酰基甘油激酶，膜联蛋白疾病和维生素D结合蛋白。我们的研究队列将由40个非洲裔美国家庭组成（300个个人）隔离LJP。我们将描述这些人对于许多疾病表现和宿主反应变量包括：牙周组织破坏的临床指标，特定的曲霉曲霉的基因型和宿主免疫的存在响应模式，包括血清IgG对A的反应。放线菌和中性粒细胞受体的密度（FMLP）和表面蛋白（GP1 10）评估非洲的异质性美国LJP人口。然后，我们将进行连锁研究以评估特定嗜中性粒细胞风险基因在 LJP在该人群中的病因。结果将通过计算赔率（LOD）得分的成对对数以确定支持或反对每个候选标记到遗传连接到 LJP特质。支持链接的支持也将使用免费模型进行评估方法，并将包括正式的异质性分析。系统评估这些候选探针最终可以提供积极的筛选遗传易感人群的风险标记 LJP的高风险，允许早期识别，诊断和治疗。