Gene polymorphisms of immunoregulatory cytokines and angiotensin-converting enzyme in Wegener's granulomatosis.
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.
Muraközy
G
G
Research Center Borstel, Medical Hospital, Parkallee 35, 23845 Borstel, Germany.
Gaede
K I
KI
Ruprecht
B
B
Gutzeit
O
O
Schürmann
M
M
Schnabel
A
A
Schlaak
M
M
Gross
W L
WL
Müller-Quernheim
J
J
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003062:Codon; D016207:Cytokines / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D014890:Granulomatosis with Polyangiitis / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D007438:Introns; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D003062:Codon; D016207:Cytokines; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007703:Peptidyl-Dipeptidase A