Association study of asthma and atopy traits and chromosome 5q cytokine cluster markers.
BACKGROUND
Linkage studies have provided evidence for the presence of gene(s) in the 5q cytokine cluster region which control total serum immunoglobulin E (IgE) concentration, and bronchial hyperreactivity (BHR). However, the identification of the gene(s) involved has been confounded by the lack of power of the published linkage studies and the presence of multiple candidate genes mapped to the region.


OBJECTIVE
To define the important loci on 5q31-33 which are implicated in the control of total serum IgE and BHR through a case/control study of association.


METHODS
We performed an association study between 11 polymorphic markers (spanning the region 5q31.1-33.1) and total serum IgE and BHR traits. A case/control sample of 181 individuals was drawn from a larger set of 2415 adults, sampled at random from a district in Nottingham, UK. Half of the subjects in this case/control sample were hyperreactive to methacholine and asthmatic (cases), while the other half were non-reactive and non-asthmatic (controls). Association analysis was performed using the non-parametric chi-squared and Mann-Whitney U-tests.


RESULTS
We observed no evidence of strong allelic association between any of the above markers and the studied traits. Markers D5S404, interferon regulatory factor 1 (IRF-1) and D5S210 showed evidence of borderline association with BHR (P = 0.04, 0.03 and 0.04 respectively), and D5S404 showed borderline significance with IgE levels (P = 0.029).


CONCLUSIONS
This study presents evidence against the presence of a strong association between markers mapped to 5q31-33 and either BHR or total serum IgE. The significance of the weaker associations observed with markers D4S404, IRF-1 and D5S210 is not clear. Whether this represents a type I error secondary to multiple hypothesis testing or a true association is uncertain.
Mansur
A H
AH
Molecular Medicine Unit, St James's University Hospital, Leeds, UK.
Bishop
D T
DT
Markham
A F
AF
Britton
J
J
Morrison
J F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged
D005819:Genetic Markers; D007073:Immunoglobulin E; D004247:DNA