Loading…
Dense mapping of chromosome 12q13.12-q23.3 and linkage to asthma and atopy
Background: Asthma is a complex disease characterized by a high prevalence of allergic diathesis and the almost ubiquitous presence of upper airway disease (eg, rhinitis). Previously, we observed linkage of asthma among Afro-Caribbean families to markers in chromosome 12q, which contains a number of...
Saved in:
Published in: | Journal of allergy and clinical immunology 1999-08, Vol.104 (2), p.485-491 |
---|---|
Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Background: Asthma is a complex disease characterized by a high prevalence of allergic diathesis and the almost ubiquitous presence of upper airway disease (eg, rhinitis). Previously, we observed linkage of asthma among Afro-Caribbean families to markers in chromosome 12q, which contains a number of genes encoding for products closely related to allergic airway inflammation and disease.
Objective: To identify susceptibility loci in chromosome 12q contributing to the genetics of upper and lower airway diseases and to expand the region to include genes encoding IFN-γ (
IFNG ) and one of the signal transducers and activators of transcription (
STAT6 ), we conducted further linkage studies among 33 multiplex families.
Methods: We characterized 528 subjects from Barbados for asthma; 82% were characterized for allergic rhinitis. Two-point and multipoint linkage analysis of 22 microsatellite markers (spanning ~79 centimorgan) was performed.
Results: Affected sib-pair analysis revealed significant evidence for linkage to asthma over approximately 30 cM (
P < .05 to .002), with the best evidence for linkage at a CA repeat polymorphism in the first intron of
IFNG in 12q21.1 (
P = .002). Evidence of linkage to allergic rhinitis was observed in the same region (
D12S313 ,
P = 0.006, and
IFNGCA ,
P = .01, respectively). Multipoint linkage analysis also provided evidence for linkage to asthma, with the best nonparametric linkage analysis score at
D12S326 (nonparametric linkage score = 3.8,
P = .0008). Modest evidence for linkage to allergic rhinitis was observed next to
D12S326 at
D12S1052 (
P = .036).
Conclusions: Our findings suggest that (1) one or more loci in the chromosome 12q13.12–q23.3 region are contributing to the expression of the clinical phenotype asthma and the strongest evidence for linkage is in a region near the gene encoding
IFNG and (2) a susceptibility locus for both asthma and allergic rhinitis maps to this region. (J Allergy Clin Immunol 1999;104:485-91.) |
---|---|
ISSN: | 0091-6749 1097-6825 |
DOI: | 10.1016/S0091-6749(99)70398-2 |