Vol. 77, June 2009

DNase I Activity and Gene Polymorphism: Role in SLE Susceptibility and Auto-Antibody Production

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DNase I Activity and Gene Polymorphism: Role in SLE Susceptibility and Auto-Antibody Production,NEHAD A. MOSAAD, GIHAN A. SLEEM and HANAN H. AHMAD

 

Abstract
Background: Previous studies have suggested that inter-rupted clearance of nuclear DNA-protein complexes after cell death might initiate and propagate systemic lupus erythema-tosus (SLE). Deoxyribonuclease I (DNase I) may be respon-sible for the removal of DNA from nuclear antigens at sites of high cell turnover, thus preventing the onset of SLE.
Objectives: To investigate the association of serum DNase I activity and single nucleotide polymorphism (SNP) +2373A>G (Gln244Arg) of DNase I gene with susceptibility to systemic lupus erythematosus (SLE) and the production of auto-antibodies to double-stranded DNA.
Subjects and Methods: A total of 42 SLE patients, all fulfilled the revised criteria of the American College of Rheumatology for the diagnosis of SLE, were enrolled in the study and 17 healthy individuals with matching age and sex as a control group, 27 out of the 42 SLE patients had lupus nephritis proved by renal biopsy. DNase I gene +2373A>G SNP was studied by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Serum DNase I activity (measured as percent of activity reduction; %AR) and anti-double-stranded DNA (anti ds-DNA) level were determined by solid phase enzyme immunoassay (ELISA).
Results: There was a significant decrease in DNase I enzyme activity (increase %AR) in the sera of SLE patients compared to the healthy individuals (p=0.000). Anti ds-DNA antibody level was significantly higher in SLE patients com-pared to control group (p=0.000). There was a significant positive correlation between DNase I enzyme (%AR) and the level of anti ds-DNA antibody (r=0.596, p=0.000). Comparing the results of lupus patients with and without nephritis revealed an increase in both DNase enzyme %AR and the level of Anti ds-DNA antibody in the nephritis group but the difference is not statistically significant. There was no association of the +2373A>G SNP genotypes or alleles with SLE susceptibility. However, SLE patients with GG genotype showed significant increase in both DNase I %AR (p=0.007) and anti ds-DNA antibody level (p=0.022) than those with AG & AA genotypes.
Conclusion: The observed association of +2373A>G SNP of DNase I gene with DNase I activity and production of anti ds-DNA antibodies but not with SLE susceptibility calls into question how this SNP could contribute to SLE pathogenesis.
A wider scale study with special emphasis on other auto-antibodies and genetic polymorphisms is recommended.

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