Polymorphisms in the IL4, IL4RA, and FCERIB genes and asthma severity.
BACKGROUND
Genetic polymorphisms have been associated with asthma and asthma severity.


OBJECTIVE
We sought to determine whether 3 polymorphisms were associated with severe asthma indicated either by the occurrence of a fatal (or near-fatal) asthma attack or by severe airflow obstruction.


METHODS
We obtained DNA and clinical data from asthmatic subjects who either died or nearly died during an asthma attack and from a group of subjects with mild-to-moderate asthma who had never experienced a fatal or near-fatal asthma episode. These groups were compared with a group of nonatopic nonasthmatic control subjects. The level of airflow obstruction (FEV(1) percent predicted) in the subjects with mild-to-moderate asthma was used as an additional measure of disease severity. The subjects were genotyped for the IL4*C-589T promoter polymorphism and the IL4RA*Q576R and the FCERIB*E237G amino acid substitutions.


RESULTS
The results showed that the FCERIB*E237G and IL4RA*Q576R polymorphisms were not associated with fatal or near-fatal asthma. However, the IL4*-589T allele was significantly increased in the subjects with fatal or near-fatal asthma compared with nonasthmatic subjects (odds ratio [OR], 1.8; P =.02) and subjects with mild-to-moderate asthma (OR, 1.9; P =.02). There was no interaction between the IL4*-589T and IL4RA*576R alleles. Of the 3 polymorphisms, only the IL4RA*576R allele was associated with severe airflow obstruction (OR, 8.2; P =.01).


CONCLUSIONS
These data suggest that the IL4*-589T allele is a risk factor for life-threatening asthma and that the IL4RA*576R allele is a risk factor for a low level of lung function in asthmatic subjects.
Sandford
A J
AJ
UBC Pulmonary Research Laboratory, St Paul's Hospital, Vancouver, UBC British Columbia, Canada.
Chagani
T
T
Zhu
S
S
Weir
T D
TD
Bai
T R
TR
Spinelli
J J
JJ
Fitzgerald
J M
JM
Behbehani
N A
NA
Tan
W C
WC
Paré
P D
PD
D000402:Airway Obstruction / Q000209:etiology; D001249:Asthma / Q000150:complications / Q000235:genetics*; D005260:Female; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D017455:Receptors, IgE / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics*
D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D015847:Interleukin-4