Different gender-associated genotype risks of Wegener's granulomatosis and microscopic polyangiitis

Zoltán Bártfai, Karoline I. Gaede, Kimberly A. Russell, Gabriella Muraközy, Joachim Müller-Quernheim, Ulrich Specks

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are systemic small vessel vasculitides associated with ANCA (AAV). Predominant Th1 and Th2 cytokine patterns have been reported for WG and MPA, respectively. Consequently, genotypes suppressing Th1 responses or augmenting Th2 responses may be more frequent in MPA than in WG. Transforming growth β1 (TGF-β1) and interleukin-10 (IL-10) genes may modify the course of vasculitis. Therefore, we investigated associations between genotype frequencies of functional polymorphisms of these cytokine genes and clinical manifestations in AAV. One hundred sixty-one AAV patients and 153 healthy blood donors were genotyped for the biallelic polymorphism in codon 25 of the TGF-β1 gene and the biallelic polymorphism at position -1082 of the IL-10 gene. No difference was found for TGF-β1 codon 25 polymorphism between control and patient groups. In contrast, a significant shift toward the homozygous AA genotype of the IL-10 (-1082) polymorphism was found in WG (25%, p < 0.005) and MPA patients (39%; p < 0.00001) compared to controls (10.5%). Furthermore, in MPA the AA homozygous genotype was significantly more frequent in females (62.5%) compared to males (20%, p < 0.05). A contribution of the TGF-β1 codon 25 polymorphism to the susceptibility-defining genetic backgrounds of AAV appears unlikely. In contrast, our findings suggest a role of the enhanced IL-10 (-1082) PM in WG and MPA with a significant gender difference in MPA.

Original languageEnglish (US)
Pages (from-to)330-337
Number of pages8
JournalClinical Immunology
Volume109
Issue number3
DOIs
StatePublished - Dec 2003

Keywords

  • ANCA
  • Gender risk
  • Gene polymorphism
  • Interleukin-10
  • Microscopic polyangiitis
  • Systemic vasculitis
  • Wegener's granulomatosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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