FRI0088 Poly(adp-ribose) polymerase (parp) polymorphism in spanish systemic lupus erythematosus (sle) patients

Background PARP is a DNA-binding protein that catalyses the covalent addition of ADP-ribose to many nuclear proteins. It is involved in DNA repair and apoptosis, processes that have been implicated as causative factors for SLE. It has been shown that patients suffering SLE have decreased PARP mRNA levels and a low enzime activity. The PARP gene is located at 1q41-q42 and contains a microsatellite (CA)n polymorphism in the promoter region that probably affects the transcription and mRNA levels. A recent study found preferential transmission of the allele containing 12 CA repeats to affected offspring in Caucasian SLE families. Objectives To investigate the association between PARP polymorphism and SLE susceptibility in Spaniards. Methods 76 unrelated SLE patients from Canary Islands (Spain) fulfilling at least four of the ACR criteria and 79 sex-matched healthy donors were included. A segment of the PARP gene containing the microsatellite was amplified by PCR and the resulting products were electrophoresed in denaturing polyacrilamide gels. Chi-square test was used for statistical analysis. Results Allelic distributions of PARP polymorphism showed no statistical differences between SLE patients and controls. But considering particular clinical features we found several associations with specific alleles: a) homozygotes for 11rep. allele suffered more lymphopenia (p = 0.04) but less hypocomplementemia (p = 0.03), b) autoantibodies anti-Ro/La were more frequent (p = 0.02) in carriers of 15rep., c) carriers of 16rep. allele presented more malar rash (p = 0.03) and seizures (p = 0.04), and finally d) carriers of 17rep. allele showed a reduced risk of production of several autoantibodies as anti-Sm (p = 0.007) and anti-Ro/La (p = 0.04). Conclusion Although PARP alleles seem not to influence susceptibility to SLE in Spaniards, some of them may be related to the presence of several clinical and analytical manifestations of the disease.