阿司匹林诱发荨麻疹和白三烯C4合酶等位基因变异的家族性聚集  

Familial aggregation of aspirin-induced urticaria and leukotriene C4 synthase allelic variant

作　　者：Mastalerz L. Setkowicz M. Sanak M. A. Szczeklik 王琼 

机构地区：[1]Department of Medicine, Jagiellonian University, School of Medicine, Skawińska 8, 31-066 Kraków, Poland

出　　处：《世界核心医学期刊文摘（皮肤病学分册）》2006年第6期21-22,共2页Digest of the World Core Medical JOurnals:Dermatology

摘　　要：Background: We have reported that in patients with chronic idiopathic urticaria (CIU) who reacted adversely to aspirin, the frequency of the -444C allele of the leukotriene C4 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 Stransferase 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-444C 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.Background： We have reported that in patients with chronic idiopathic urticaria （CIU） who reacted adversely to as pirin, the frequency of the -444C allele of the leukotriene C4 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 Stransferase 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-444C 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.

关 键 词：慢性特发性荨麻疹 阿司匹林耐受 等位基因变异 白三烯C4 家族性 GSTM1基因缺失 谷胱甘肽转移酶M1 聚集 诱发 基因型变异 

分 类 号：R758.24[医药卫生—皮肤病学与性病学] R542.22[医药卫生—临床医学]