Pe. Graves et al., A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children, J ALLERG CL, 105(3), 2000, pp. 506-513
Background: Increased levels of total serum IgE are a strong risk factor fo
r the development of asthma. IgE is also involved in host defenses against
parasites and fungi. Linkage of total serum IgE with markers located close
to the 3 Mb cluster of cytokine genes in chromosome 5q31 has been reported.
IL-4 or IL-13 are regarded as essential for IgE synthesis.
Objective: We tested whether polymorphisms in the IL-13 gene might explain
the linkage between chromosome 5q31 and total serum IgE levels.
Methods: We used denaturing HPLC to detect polymorphisms in overlapping PCR
fragments of the IL-13 gene including promoter and 3' untranslated regions
, After sequencing was performed to identify the locations of the polymorph
isms, PCR and primer-induced restriction site assays were used to genotype
subjects in 3 unselected populations,
Results: We report here 7 polymorphisms (6 novel) in IL-13. Four of these p
olymorphisms are tightly linked to a variant in the terminal portion of the
coding region of the gene that results in a predicted amino acid change in
residue 130 (Arg130Gln). The Gin form is strongly associated (P = .000002)
with increased serum IgE levels in 3 different populations comprising a to
tal of 1399 children. Two additional polymorphisms in the promoter region o
f IL-13 are more loosely linked to Arg130Gln and are also less significantl
y associated with total serum IgE levels.
Conclusion: These data suggest that the Arg130Gln pol;morphism in IL-13, or
others in close linkage with it, is associated with the development of the
elevated serum IgE phenotype.