Genetic Predisposition to Latex Allergy: Role of Interleukin 13 and Interleukin 18

Background:Occupational exposure of healthcare workers to natural rubber latex has led to sensitization and potentially life-threatening anaphylaxis. Although environmental exposure to natural rubber latex products is necessary for sensitization, it is not sufficient. A number of genetic factors also seem to contribute to the latex sensitization; however, the multigenic nature of the allergic phenotype has made the identification of susceptibility genes difficult. The current study tests the hypothesis that known functional polymorphisms in genes encoding interleukin 4, interleukin 13, and interleukin 18 occur in a higher frequency in healthcare workers with natural rubber latex allergy. Methods:Four hundred thirty-two healthcare workers with occupational exposure to natural rubber latex were screened using a clinical history questionnaire and latex-specific immunoglobulin E serology. Genomic DNA was extracted from peripheral blood lymphocytes and analyzed for single-nucleotide polymorphisms in candidate genes of interest. Data from cases and controls were analyzed by nominal logistic regression, with P < 0.05 considered significant. Results:The latex allergy phenotype was significantly associated with promoter polymorphisms in IL13 −1055 (P = 0.02), IL18 −607 (P = 0.02), and IL18 −656 (P = 0.02) compared with nonatopic controls. Conclusions:The significant association of IL13 and IL18 promoter polymorphisms with latex allergy suggests a potential location for genetic control in the induction of latex allergy in individuals and extends the understanding of the genetic basis for the induction of immediate-type hypersensitivity in healthcare workers occupationally exposed to natural rubber latex.

[1]  D. Ownby,et al.  A review of natural-rubber latex allergy in health care workers. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  S. Weiland,et al.  A complete screening of the IL4 gene: novel polymorphisms and their association with asthma and IgE in childhood. , 2003, The Journal of allergy and clinical immunology.

[3]  Tom R. Gaunt,et al.  Polymorphisms in the interleukin‐4 and interleukin‐4 receptor α chain genes confer susceptibility to asthma and atopy in a Caucasian population , 2003, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[4]  J. Bertrand,et al.  Effect of TNF and LTA polymorphisms on biological markers of response to oxidative stimuli in coal miners: a model of gene-environment interaction , 2003, Journal of medical genetics.

[5]  T. Kurz,et al.  Polymorphisms in the IL 18 gene are associated with specific sensitization to common allergens and allergic rhinitis. , 2003, The Journal of allergy and clinical immunology.

[6]  C. Ober,et al.  Present status on the genetic studies of asthma. , 2002, Current opinion in immunology.

[7]  A. Krętowski,et al.  Interleukin-18 promoter polymorphisms in type 1 diabetes. , 2002, Diabetes.

[8]  Santa Jeremy Ono,et al.  Genomics and proteomics of allergic disease , 2002, Immunology.

[9]  I. Kinalska,et al.  Interleukin-18 Promoter Polymorphisms in Type 1 , 2002 .

[10]  E. Krieg,et al.  Receiver Operating Characteristics Analyses of Food and Drug Administration-Cleared Serological Assays for Natural Rubber Latex-Specific Immunoglobulin E Antibody , 2001, Clinical Diagnostic Laboratory Immunology.

[11]  V. Giedraitis,et al.  Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation , 2001, Journal of Neuroimmunology.

[12]  R. Geha,et al.  Molecular mechanisms of IgE regulation. , 2000, The Journal of allergy and clinical immunology.

[13]  S. Akira,et al.  IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  E. Groot,et al.  An IL-13 promoter polymorphism associated with increased risk of allergic asthma , 1999, Genes and Immunity.

[15]  C. Dinarello IL-18: A TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. , 1999, The Journal of allergy and clinical immunology.

[16]  R. Hamilton,et al.  Prevalence of Latex Allergy among Anesthesiologists: Identification of Sensitized but Asymptomatic Individuals , 1998, Anesthesiology.

[17]  W. Cookson,et al.  Investigation of an interleukin-4 promoter polymorphism for associations with asthma and atopy. , 1996, Journal of medical genetics.

[18]  M. Klinnert,et al.  Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy , 1995, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[19]  G. Assmann,et al.  Mutagenically separated PCR (MS-PCR): a highly specific one step procedure for easy mutation detection. , 1993, Nucleic acids research.

[20]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[21]  M. Johns,et al.  Purification of human genomic DNA from whole blood using sodium perchlorate in place of phenol. , 1989, Analytical biochemistry.