title: Interleukin-13 promoter gene polymorphism -1112C/T is associated with the systemic form of mastocytosis.
abstract: BACKGROUND
  Mastocytosis is a heterogenous disease involving mast cells (MC) and their progenitors. Cutaneous and systemic variants of the disease have been reported. In contrast to cutaneous mastocytosis (CM), patients with systemic mastocytosis (SM) are at risk to develop disease progression or a nonMC-lineage haematopoietic neoplasm. Little is known, however, about factors predisposing for the development of SM. One factor may be cytokine regulation of MC progenitors.
  
  
  METHODS
  We examined the role of the interleukin-13 (IL-13) promoter gene polymorphism -1112C/T, known to be associated with increased transcription, in mastocytosis using allele-specific polymerase chain reaction method. Serum tryptase and IL-13 levels were determined by immunoassay, and expression of the IL-13 receptor in neoplastic MC by reverse transcription-polymerase chain reaction and flow cytometry.
  
  
  RESULTS
  The frequency of the -1112T allele of the IL-13 promoter was significantly higher in patients with SM compared with CM (P < 0.008) and in mastocytosis patients compared with healthy controls (P < 0.0001). Correspondingly, the polymorphism was found to correlate with an elevated serum tryptase level (P = 0.004) and with adult-onset of the disease (P < 0.0015), both of which are almost invariably associated with SM. Serum IL-13 levels were also higher in SM patients compared with CM (P = 0.011), and higher in CT- than in CC carriers (P < 0.05). Finally, we were able to show that neoplastic human MC display IL-13 receptors and grow better in IL-13-containing medium.
  
  
  CONCLUSIONS
  The -1112C/T IL-13 gene polymorphism and the resulting 'hypertranscription' may predispose for the development of SM.
authors.affiliation: Department of Dermatology, Medical university of Gdańsk. Gdańsk, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Nedoszytko
authors.forename: M
authors.initials: M
authors.lastname: Niedoszytko
authors.forename: M
authors.initials: M
authors.lastname: Lange
authors.forename: J
authors.initials: J
authors.lastname: van Doormaal
authors.forename: J
authors.initials: J
authors.lastname: Gleń
authors.forename: M
authors.initials: M
authors.lastname: Zabłotna
authors.forename: J
authors.initials: J
authors.lastname: Renke
authors.forename: A
authors.initials: A
authors.lastname: Vales
authors.forename: F
authors.initials: F
authors.lastname: Buljubasic
authors.forename: E
authors.initials: E
authors.lastname: Jassem
authors.forename: J
authors.initials: J
authors.lastname: Roszkiewicz
authors.forename: P
authors.initials: P
authors.lastname: Valent
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D018793:Interleukin-13 / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D034721:Mastocytosis, Systemic / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D053660:Receptors, Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053802:Tryptases / Q000097:blood / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D018793:Interleukin-13; D053660:Receptors, Interleukin-13; D053802:Tryptases