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Familial aggregation of aspirin-induced urticaria and leukotriene C synthase allelic variant
L Mastalerz1, M Setkowicz, M Sanak
1Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland.
Insights
Aspirin-induced urticaria (AIU) aggregates in families with the leukotriene C(4) synthase gene (-444)C allele. All AIU patients in this study also had a deletion in the glutathione S-transferase M1 gene.
Area of Science:
- Immunology
- Genetics
- Pharmacology
Background:
- Chronic idiopathic urticaria (CIU) patients with adverse aspirin reactions show higher frequency of the leukotriene C(4) synthase gene (-444)C allele.
- This suggests a potential genetic link in aspirin hypersensitivity.
Purpose of the Study:
- Investigate the inheritance pattern of aspirin-induced urticaria (AIU) in two families.
- Analyze polymorphisms in leukotriene C(4) synthase (LTC4S), glutathione S-transferase M1 (GSTM1), and glutathione S-transferase P1 (GSTP1) genes in relation to AIU.
Main Methods:
- Conducted oral aspirin challenge tests on family members of CIU patients with a history of aspirin intolerance.
- Performed genomic DNA analysis to determine LTC4S, GSTM1, and GSTP1 gene polymorphisms.
Main Results:
- AIU was confirmed in 3/5 individuals in Family 1 and 2/7 in Family 2 via aspirin challenge.
- Variant LTC4S genotypes (AC or CC) were found in parents, with AIU present in affected children carrying these genotypes.
- Deletion of the GSTM1 gene was observed in all individuals with a positive aspirin challenge test.
Conclusions:
- Aspirin-induced urticaria aggregates in families inheriting the LTC4S (-444)C allele.
- Aspirin sensitivity inheritance in these families does not follow a simple Mendelian pattern.
- GSTM1 gene deletion is a common factor in all ascertained AIU individuals in this study.
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.
Objectives:
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.
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