Polymorphisms in the interleukin-1 gene influence the stratum corneum interleukin-1 alpha concentration in uninvolved skin of patients with chronic irritant contact dermatitis.
BACKGROUND
Interleukin (IL)-1 alpha and its receptor antagonist IL-1 ra play a role in skin inflammation. Several polymorphisms in the IL1 gene cluster, coding for IL-1 alpha, IL-1 ra, and IL-1 beta, influence their protein expression. Within this cluster, strong linkage disequilibrium has been shown.


OBJECTIVE
We studied the association between the polymorphisms IL1A-889 (C-->T) and IL1B-31 (T-->C) and the concentration of IL-1 alpha and IL-1 ra in the stratum corneum (SC).


METHODS
In 124 patients with chronic irritant contact dermatitis, we genotyped the IL1A-889 and IL1B-31 polymorphisms and determined the amount of IL-1 alpha and IL-1 ra on tape strips obtained from uninvolved skin of the volar forearm.


RESULTS
The SC IL-1 alpha concentration was 23% and 47% lower in subjects with IL1A-889 C/T genotype and T/T genotype, respectively, compared with wild-type genotype. In subjects with IL1B-31 C/C genotype, the IL-1 alpha concentration was 51% lower compared with C/T and T/T genotypes. The ratio IL-1 ra/IL-1 alpha increased twofold in IL1A-889 C/T genotype and threefold in T/T genotype compared with wild type.


CONCLUSIONS
We have shown a clear effect of IL1 genotype on protein expression in the SC. This altered expression may be responsible for the interindividual differences in the inflammatory response of the skin.
de Jongh
Cindy M
CM
Coronel Institute of Occupational Health, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
Khrenova
Liubov
L
Kezic
Sanja
S
Rustemeyer
Thomas
T
Verberk
Maarten M
MM
John
Swen M
SM
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D002908:Chronic Disease; D004247:DNA / Q000032:analysis; D017453:Dermatitis, Irritant / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D004247:DNA