Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population.
BACKGROUND
IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype.


OBJECTIVE
To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Ralpha chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma.


METHODS
Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Ralpha chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England.


RESULTS
Case-control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006).


CONCLUSIONS
Our data suggest that polymorphisms in the IL-4 and IL-4Ralpha chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.
Beghé
B
B
Divisions of Human Genetics Infection, Inflammation and Repair, School of Medicine, University of Southampton, UK. bianca.beghe@unipd.it
Barton
S
S
Rorke
S
S
Peng
Q
Q
Sayers
I
I
Gaunt
T
T
Keith
T P
TP
Clough
J B
JB
Holgate
S T
ST
Holloway
J W
JW
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D013223:Statistics as Topic
D019948:Receptors, Interleukin-4; D015847:Interleukin-4