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A major genomic region involved in Wegener's granulomatosis includes the gene for retinoid receptor beta ( RXRB ) which forms heterodimers with peroxisome proliferator-activated receptors (PPARs). It is unclear whether this association directly arises from the  RXRB  allele(s) or via a linked variation. In order to reveal any hitherto unknown and potentially disease-relevant variation of the  RXRB  gene, we have genotyped four tagging SNPs of this genomic region and have directly sequenced selected WG patients and controls representing disease-associated haplotypes. Additionally, we have genotyped 2 SNPs each in the genes for PPAR α  and PPAR γ  ( PPARA  and  PPARG ). Hence, we confirmed the strong association of the  RXRB  locus with WG but could not reveal any novel variation in  RXRB . None of the  PPARA  and  PPARG  SNPs showed association with WG. Moreover, no epistatic effect was seen between  RXRB  and  PPARA / PPARG  alleles.  These results do not support an etiopathological role of PPAR in WG. Analyses of further genes functionally linked to RXRB may provide additional data useful to evaluate the  RXRB  association found in WG.

Genetic Variability of RXRB, PPARA, and PPARG in Wegener's Granulomatosis