ACQUIRED & GENETIC DETERMINANTS OF MULTIPLE SCLEROSIS

获得

• 批准号: 6793552
• 负责人: THOMAS McCulloch MACK
• 金额: $ 59.73万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6793552
• 关键词: Herpesviridae disease; chlamydial disease; disease /disorder etiology; disease /disorder onset; estrogens; family genetics; gene environment interaction; genetic polymorphism; genetic susceptibility; histocompatibility antigens; human subject; immunogenetics; major histocompatibility complex; medical records; multiple sclerosis; myelin basic proteins; nervous system disorder epidemiology; patient oriented research; remission /regression; twin /multiplet

The long-term goal of this proposal is to identify links between specific environmental exposures and/or specific gene alleles, and multiple sclerosis onset and progression. A cohort of 1294 pairs of North American twins affected by multiple sclerosis was assembled from 1980-92, detailed medical records, exposure and disability information were gathered independently from affected and unaffected individuals, and follow-up for new diagnoses and new records has subsequently proceeded. An additional set of 195 pairs of affected California native resident twins has been identified within a cohort of 41,000 twins participating in a population-based registry. The up-date on all cases will be completed, diagnoses will be systematically validated using the additional records, and age-specific disability information will be gathered. Blood specimens from both members of each pair and from specific family members as controls will be collected. The affected twins will be compared to their unaffected co-twins with respect to historical evidence of infection and other exposures and characteristics such as reproductive evidences of endogenous estrogen production. Cases will be compared to both co-twins and family member controls with respect to serological evidence of past infection with Chlamydia pneumoniae and members of the herpes virus family. We will compare cases to relatives with respect to the prevalence of alleles at the HLA (DR) locus as well as at various other candidate loci, found by genome-wide screening or that affect immune competence, myelin basic protein, and other pertinent functions. Within the set of cases only, both environmental and genetic factors will be assessed as determinants of age at onset and age-specific progression. If links to both acquired exposure and genome are identified, given adequate power, specific gene- environment interactions will be assessed. Analyses for both etiology and progression will consist of logistic regression and sub-analyses stratified on gender, zygosity, and HLA (DR) status. Additional descriptive evidence of environmental etiology will also be sought.

该提案的长期目标是确定特定环境暴露与/或特定基因等位基因以及多发性硬化症的发作和进展之间的联系。 从1980 - 92年组建了一组1294对受多发性硬化症影响的北美双胞胎，详细的医疗记录，暴露和残疾信息是独立于受影响和不受影响的人收集的，并随后进行了新记录，随后进行了新记录。 。 在参加基于人群的注册表的41,000个双胞胎中，已经确定了另外一组195对受影响的加利福尼亚州本地居民双胞胎。 所有情况的最新情况都将完成，将使用其他记录系统地验证诊断，并收集特定年龄的残疾信息。 将收集来自每一对的两个成员和特定家庭成员作为对照的血液标本。 就感染的历史证据以及其他暴露和特征，例如内源性雌激素产生的生殖证据，将被影响的双胞胎与未受影响的共晶体进行比较。 就肺炎衣原体感染的血清学证据和疱疹病毒家族的成员，将病例与共同双胞胎和家庭成员对照进行比较。 我们将将病例与亲戚在HLA（DR）基因座以及其他各种候选基因座（通过全基因组筛查或影响免疫能力，髓磷脂碱性蛋白质和其他相关功能）中进行比较。 仅在一组情况下，环境和遗传因素都将被评估为发病和特定年龄进展时年龄的决定因素。 如果确定了与获得足够功能的链接，则将评估特定的基因环境相互作用。 对病因和进展的分析将包括逻辑回归和分层在性别，Zygosity和HLA（DR）状态下的子分析。还将寻求其他描述性证据的证据。