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Home > "C" Clinical Trials Conditions > Characterizing a 5P-Linked BHR Susceptibility Locus  Characterizing a 5P-Linked BHR Susceptibility Locus
Characterizing a 5P-Linked BHR Susceptibility Locus
For Condition: Asthma,Lung Diseases
Status: No longer recruiting
Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) ,
Synopsis: To identify the predisposing genes responsible for asthma and bronchial hyperresponsiveness (BHR) at region 5p13.3 in an inbred Hutterite community.
Details: BACKGROUND: Asthma is the most common chronic disease in industrialized nations, affecting more than10 million people in the U.S. alone. Familial aggregation and concordance rates in monozygotic twins have suggested a genetic component to asthma. Dr. Ober and colleagues have been conducting studies on the genetics of asthma and atopy in the Hutterites, an inbred population of European origins that practices a communal lifestyle. A genome-wide screen with 564 markers (average spacing 6 cM) was completed in an extended pedigree of 717 Hutterites who were well characterized with respect to asthma, atopy, and related phenotypes. These individuals are descendants of only 64 ancestors who lived in the early 1700's to the early 1800's. Evidence for linkage with bronchial hyperresponsiveness (BHR) by the likelihood ratio test extended over 30 centimorgans (cM) on chromosome 5p, with P-values as small as 0.001. Additional evidence for linkage at this same location was evident by the transmission disequilibrium test (P=0.0061). Typing additional markers in this region identified a critical region of 2.4 cM, corresponding to 1.5 Mb of DNA, and a high risk haplotype that is over transmitted to affected individuals. The study is in response to a Request for Applications, "Positional Candidate Approaches in Asthma Gene Discovery" released in Ocatober, 1999. DESIGN NARRATIVE: Dr. Ober and colleagues are characterizing the 5p-linked BHR susceptibility locus in the inbred Hutterites by positional cloning and replicating these findings in outbred, ethnically diverse populations. They are examining single nucleotide polymorphisms (SNPs) spaced about 10 kb apart in each gene, and assessing the evidence for over transmission to affected offspring with each SNP and SNP haplotypes. Associations in the Hutterites will be replicated in two outbred samples (a Caucasian sample from Germany, and an African American sample from Chicago). The functional effects of associated variants will be assessed by in vitro assays as well as by genotype-phenotype studies in outbred samples that have been evaluated for asthma and atopy phenotypes. Identifying asthma or BHR susceptibility loci may identify novel pathways in asthma pathogenesis, thereby allowing for the development of new therapies and intervention strategies for these common diseases.
Eligibility:
Study Type: Observational, Natural History
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: No eligibility criteria
Total Enrollment:
Location and Contact Information:
Additional Information:
Study ID Numbers: 948;
Study Start Date: September 2000
Record last reviewed: January 2004
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00006512
Other Lung Diseases Studies:
1. Asthma Partnership for Minority Children
2. Asthma Clinical Research Network (ACRN)
3. Inhaled NO for the Prevention of Chronic Lung Disease
4. Pulmonary Hypertension--Mechanisms and Family Registry
5. High Frequency Ventilation in Premature Infants (HIFI)
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Characterizing a 5P-Linked BHR Susceptibility Locus
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