Familial aggregation of aspirin-induced urticaria and leukotriene C synthase allelic variant.
BACKGROUND
We have reported that in patients with chronic idiopathic urticaria (CIU) who reacted adversely to aspirin, the frequency of the (-444)C allele of the leukotriene C(4) synthase gene (LTC4S) was higher than in patients who tolerated aspirin well.


OBJECTIVE
To study the pattern of aspirin-induced urticaria (AIU) in two families, with special interest on the polymorphisms of LTC4S (AA, AC, CC) and the glutathione S-transferase M1 and P1 genes (GSTM1 and GSTP1).


METHODS
Of 74 patients with CIU and a history of aspirin hypersensitivity studied by us, two patients (probands) gave a family history of aspirin intolerance. Oral challenge tests with aspirin were carried out in members of these families. Genomic DNA samples were obtained from peripheral blood to study the polymorphisms of LTC4S, GSTM1 and GSTP1.


RESULTS
In family 1 the aspirin challenge test confirmed AIU in three of five (60%) individuals, but in family 2 only in two of seven (29%). In both families, the variant genotypes of LTC4S (AC or CC) were present in the parents, but only one of them had CIU. In family 1, with both parents healthy, the three children had AIU; in two it was associated with variant LTC4S genotype. In family 2, urticaria following aspirin ingestion was present only with variant LTC4S genotype. In patients of both families with positive aspirin challenge test, deletion of the GSTM1 gene was present.


CONCLUSIONS
AIU aggregates in families inheriting the LTC4S(-444)C allele. Segregation of aspirin sensitivity in these families does not follow a clear Mendelian pattern. A common deletion of GSTM1, one of several enzymes involved in conjugation of a wide range of electrophilic substances with glutathione, was present in all individuals ascertained to have AIU.
Mastalerz
L
L
Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland.
Setkowicz
M
M
Sanak
M
M
Rybarczyk
H
H
Szczeklik
A
A
D000328:Adult; D000368:Aged; D000483:Alleles; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D003875:Drug Eruptions / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D016037:Single-Blind Method; D014581:Urticaria / Q000139:chemically induced / Q000235:genetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D016861:Cyclooxygenase Inhibitors; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496556:GSTP1 protein, human; C041116:leukotriene-C4 synthase