Gluten Sensitivity in the Old Order Amish

旧秩序阿米什人对麸质的敏感性

• 批准号: 6774591
• 负责人: DANIEL J MCBRIDE
• 金额: $ 14.85万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6774591
• 关键词: Mennonite; biomarker; celiac disease; clinical research; epidemiology; family genetics; genetic screening; human subject; immunoglobulin A; medical outreach /case finding; phenotype; protein glutamine gamma glutamyltransferase; questionnaires; serology /serodiagnosis

DESCRIPTION (provided by applicant): Gluten-sensitive enteropathy (GSE; VIM 607202) or celiac disease (CD; MIM 212750) has been well recognized as a public health concern for some time in Europe. During the last 10-15 years gluten sensitive enteropathy (GSE) has become better recognized in the United States as a serious, but under-diagnosed health problem, with recent estimates of its prevalence in the general U.S. population ranging from 1:135 to 1:250. The purpose of this pilot study is to demonstrate the presence of GSE in the Amish with the ultimate goal in a future application to identify susceptibility loci for GSE in this genetically homogenous population. The Old Order Amish can trace their ancestry to a limited number of founder couples who emigrated from Europe in the early 1700's. The deep pedigree structure, large families, longevity, and the homogeneous life-style of the Amish will be major advantages for genome-wide linkage and association analysis. GSE is a complex immunogenetic disorder due to intolerance to dietary prolamins found in wheat, barley, and rye. In genetically susceptible individuals, ingestion of the prolamins elicits an inflammatory injury to the small intestine with villous atrophy and consequent malabsorption. The clinical signs and symptoms range from overt to silent. Treatment with a life-long gluten-free diet (GFD) typically reverses the mucosal damage. The major histocompatibility complex class II alleles DQA1*0501 and DQB*0201 represent a major genetic association to the patho-physiology of GSE. The HLA-DQ2 allelic combination is found in >90% of celiac patients from northern Europe. However, the variable penetrance, 30%-50% concordance for GSE in HLA identical siblings, and near 100% concordance in monozygotic twins suggests a major patho-physiological role for additional gene loci. Approximately 1,200 individuals have been recruited and enrolled in the Amish Family Osteoporosis Study (AFOS). We propose to screen the existing AFOS serum and DNA samples for diagnostic biomarkers of CD in order to (1) demonstrate the presence of GSE in the Amish and (2) recruit additional family members around study subjects with positive GSE biomarker tests.

描述（由申请人提供）： 麸质敏感的肠病（GSE； VIM 607202）或乳糜泻（CD; MIM 212750）在欧洲一段时间以来一直被公认为是公共卫生问题。在过去的10 - 15年中，麸质敏感肠病（GSE）在美国变得更好地认可为严重但未诊断的健康问题，最近估计其在美国普通人群中的患病率在1：135到1：250不等。这项试验研究的目的是证明在未来应用中，在未来应用中，最终目标是识别GSE在这个遗传同质种群中的易感基因座的最终目标。旧秩序阿米什（Amish）可以将他们的祖先追溯到1700年代初从欧洲移民的有限数量的创始人夫妇。深层的血统结构，大家庭，寿命和阿米什人的同质生活方式将是全基因组联系与关联分析的主要优势。 GSE是一种复杂的免疫疾病，因为在小麦，大麦和黑麦中发现的饮食中杂素不耐受。在遗传易感的个体中，摄入略丙蛋白会引起小肠炎症性损伤，并具有绒毛萎缩并随之而来的吸收不良。临床体征和症状从明显到沉默。用终身无麸质饮食（GFD）治疗通常会逆转粘膜损伤。主要的组织相容性复合物II类等位基因DQA1*0501和DQB*0201代表了与GSE的病原体生理学的主要遗传关联。 HLA-DQ2等位基因组合在北欧的乳糜泻患者中> 90％。然而，可变的渗透率为HLA相同兄弟姐妹的GSE的30％-50％的一致性，单卵双胞胎中的一致性接近100％的一致性表明，其他基因基因座的病理学作用很重要。 大约有1,200个人被招募并参与了阿米什家族骨质疏松研究（AFOS）。我们建议筛选现有的AFOS血清和DNA样品，以进行CD的诊断生物标志物，以表明（1）在Amish中证明了GSE的存在，（2）（2）围绕具有GSE生物标志物阳性的研究受试者招募其他家庭成员。