Gene polymorphisms of immunoregulatory cytokines and angiotensin-converting enzyme in Wegener's granulomatosis

• Published in: Journal of molecular medicine (Berlin, Germany) Germany), 2001-11, Vol.79 (11), p.665-670
• Main Authors: MURAKÖZY, Gabriella, GAEDE, Karoline I, RUPRECHT, Bertram, GUTZEIT, Oliver, SCHÜRMANN, Manfred, SCHNABEL, Armin, SCHLAAK, Max, GROSS, Wolfgang L, MÜLLER-QUERNHEIM, Joachim
• Format: Article
• Language: English
• Subjects: ACE protein; Adult; Alleles; Biological and medical sciences; Case-Control Studies; Codon; Cytokines - genetics; Down-Regulation; Female; Gene Deletion; Genotype; Granulomatosis with Polyangiitis - genetics; Humans; Interleukin-10 - genetics; Introns; Male; Medical sciences; Middle Aged; Peptidyl-Dipeptidase A - genetics; Polymerase Chain Reaction; Polymorphism, Genetic; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T-Lymphocytes - metabolism; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta1
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s001090100263

Wegener's granulomatosis is a granulomatous and vasculitic disease of unknown origin. Gene polymorphisms are known to affect phenotypes of numerous diseases. Polymorphisms within the angiotensin-converting enzyme (ACE), transforming growth factor-beta1 (TGF-beta1), and interleukin-10 (IL-10) genes are suspected to modify the course of granulomatous disorders. We examined whether the genotype frequencies of the named polymorphisms differ in Wegener's granulomatosis from those in healthy controls. Thirty-nine patients with Wegener's granulomatosis were genotyped for the deletion/insertion polymorphism in intron 16 of the ACE gene, a biallelic polymorphism in codon 25 of the TGF-beta1 gene and a biallelic polymorphism at position -1082 of the IL-10 gene and compared with healthy blood donors. For the ACE polymorphism no significant differences were detected neither in the allele frequencies nor in the genotype frequencies. For TGF-beta1 a trend to genotype CG was found. The most interesting result was the observed, significant shift to genotype AA of the IL-10 polymorphism in Wegener's granulomatosis. IL-10 and TGF-beta1, immunoregulatory cytokines capable of down-regulating T helper cell type 1 response, showed a significant shift or a trend, respectively towards genotypes associated with reduced cytokine release, leading to the hypothesis that different immunoregulatory cytokine patterns dependent on gene polymorphisms might be involved in the pathogenesis of Wegener's granulomatosis.