Contribution of functional variation in the IL13 gene to allergy, hay fever and asthma in the NSHD longitudinal 1946 birth cohort.
BACKGROUND
Genetic variants of the two adjacent genes, IL13 and IL4 have frequently been reported as being associated with susceptibility to atopy and asthma, both in adults and children, and some studies also suggest association with lung function and chronic obstructive pulmonary disease.


METHODS
In this study, we examined for the first time the effect of these variants in 2918 adults in a longitudinal birth cohort, the British National Survey of Health and Development, where there are extensive life style, developmental and environmental data. We examine two IL13 single nucleotide polymorphisms (SNPs) IL13 rs20541 (R110Q) and rs1800925 (-1024C>T) and one IL4 SNP, rs2070874 (-33C>T) with likely function.


RESULTS
We show that IL13 rs20541 and rs1800925 are each significantly associated with self-reported asthma and allergy, and that this association is not confounded by any of the known developmental and environmental risk factors for asthma and atopy, including in particular place of birth. IL13 rs20541 does however act as a confounder for the IL13 rs1800925 associations, meaning that there is no statistical support for rs1800925 having an independent effect. There is nevertheless evidence for interaction between smoking and rs1800925, with allergy as outcome. None of the SNPs showed association with measures of lung function, nor any interaction with the effect of smoking on lung function.


CONCLUSIONS
In a longitudinal population cohort we have established a role for polymorphism of IL13 in determining susceptibility to both atopy and asthma.
Black
S
S
MRC Unit for Lifelong Health and Ageing, Department of Epidemiology and Public Health, Royal Free & University College London Medical School, London NW1 2HE, UK.
Teixeira
A S
AS
Loh
A X W
AX
Vinall
L
L
Holloway
J W
JW
Hardy
R
R
Swallow
D M
DM
D000328:Adult; D001249:Asthma / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D006969:Hypersensitivity, Immediate / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics; D012307:Risk Factors; D012907:Smoking; D006113:United Kingdom
D018793:Interleukin-13; D015847:Interleukin-4