The p53 G72C and MDM2 T309G single nucleotide polymorphisms in patients with Wegener's granulomatosis.
OBJECTIVE
Wegener's granulomatosis (WG) is a rare disease with unknown aetiology, but there is evidence for a complex genetic background. The tumor suppressor p53 and its most important negative regulator, MDM2, are positioned in the centre of a pathway that eliminates damaged cells through apoptosis. Furthermore, p53 is one of the most important negative regulators of the pro-inflammatory transcription factor nuclear factor kappa b (NFkappaB). In this respect the investigation of polymorphisms in the p53-network could be a promising approach contributing susceptibility of WG and its course of disease.


METHODS
A case control study with 132 patients with WG and 512 healthy blood donors was conducted to evaluate an association of p53-SNP G72C or MDM2-SNP T309G with WG. SNPs were genotyped by polymerase chain reaction (PCR) and subsequent differential enzymatic restriction. All patients showed the clinical pathological findings of WG according to the ACR classification criteria of 1990.


RESULTS
The p53 G72C and MDM2 T309G polymorphisms did not show any difference between WG patients and controls. The subgroup analysis of gender differences and earlier onset of WG (younger than median age of 51 years at diagnosis) did not show any differences in allelic or genotype frequencies of p53 G72C or MDM2 T309G SNP between WG patients and the control group.


CONCLUSIONS
Our study showed no association between the p53 SNP G72C and the MDM2 SNP T309G with susceptibility or course of disease in patients with WG. The data presented do not suggest that alterations in the p53-network play a key role in the pathogenesis of WG.
Assmann
G
G
Internal Medicine I and José-Carreras-Research Center, University of Saarland Medical School, Homburg/Saar, Germany. gunter.assmann@uniklinikum-saarland.de
Wieczorek
S
S
Wibisono
D
D
Roemer
K
K
Arning
L
L
Voswinkel
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014890:Granulomatosis with Polyangiitis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2