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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2005 Mar;64(3):457–461. doi: 10.1136/ard.2004.025809

Distinct tumour necrosis factor α, interferon γ, interleukin 10, and cytotoxic T cell antigen 4 gene polymorphisms in disease occurrence and end stage renal disease in Wegener's granulomatosis

B Spriewald 1, O Witzke 1, R Wassmuth 1, R Wenzel 1, M Arnold 1, T Philipp 1, J Kalden 1
PMCID: PMC1755422  PMID: 15708894

Abstract

Background: Cytokines and T cell regulatory proteins play an important role in the pathogenesis of Wegener's granulomatosis (WG).

Objective: To investigate cytokine and cytotoxic T cell antigen-4 (CTLA4) gene polymorphisms and HLA class II alleles in generalised WG.

Methods: The distribution of cytokine and cytotoxic T cell antigen 4 (CTLA4) gene polymorphisms and HLA class II alleles was analysed in 32 patients with generalised WG and 91 healthy controls. Genotyping was carried out for HLA-DRB1 and HLA-DQB1 and for polymorphism of the genes encoding TNFα (–238, –308, –376), TGFß (codon 10 and 25), IFNγ (+874), IL6 (–174), IL10 (–592, –819, –1082), CTLA4 (–318, +49), and the (AT)n repeats of the CTLA4 gene. In addition, stratification analysis was carried out according to the presence (n = 15) or absence (n = 17) of end stage renal disease.

Results: An increase in the IFNγ +874 T/T (odds ratio (OR) = 3.14) and TNFα –238 G/A (OR = 5.01) genotypes was found in WG patients. When ESRD positive and negative patients were compared, the IFNγ +874 A/A and the CTLA4 –318 C/C genotypes were found more often in the ESRD subgroup (OR = 10.6 and OR = 2.25). WG patients without ESRD had a higher frequency of the IL10 GCC/ACC promotor genotype (OR = 0.13) and long CTLA4 (AT)n repeats (OR = 0.4). No effect was seen for HLA-DR and –DQ markers.

Conclusions: Disease susceptibility and clinical course in WG may be associated with distinct polymorphisms of cytokine and CTLA4 genes.

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Selected References

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