Association of a non-synonymous single-nucleotide polymorphism of DNASEI with SLE susceptibility.
OBJECTIVE
To investigate the association of a non-synonymous single-nucleotide polymorphism (SNP) in DNASEI with susceptibility to systemic lupus erythematosus (SLE) and the production of autoantibodies to nuclear antigens.


METHODS
The Gln244Arg (rs1053874) SNP was studied in 276 SLE patients and in 368 healthy controls of Spanish ancestry. Its relationship with SLE susceptibility, serum DNase I activity, anti-ribonucleoprotein (RNP), anti-double-stranded DNA (dsDNA), anti-nucleosome and anti-single-stranded DNA (ssDNA) antibodies was determined.


RESULTS
An association of the Gln244Arg SNP with SLE susceptibility that followed a recessive genetic model (P=0.002) was found. The GG genotype was more common in SLE patients (59.8%) than in controls (47.3%). However, the Gln244Arg genotype did not correlate with DNase I activity in sera from SLE patients or from controls. In addition, the Gln244Arg SNP did not influence autoantibody titres significantly.


CONCLUSIONS
The association of the Gln244Arg SNP with SLE susceptibility indicates that common polymorphisms in DNASEI play a role in the genetics of SLE. However, the lack of effect of the Gln244Arg SNP on serum DNase I activity calls into question the direct involvement of this specific SNP.
Bodaño
A
A
Laboratorio de Investigación 5, Hospital Clínico Universitario de Santiago, 15706- Santiago de Compostela, A Coruña, Spain.
González
A
A
Ferreiros-Vidal
I
I
Balada
E
E
Ordi
J
J
Carreira
P
P
Gómez-Reino
J J
JJ
Conde
C
C
D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D003850:Deoxyribonuclease I / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide
D000974:Antibodies, Antinuclear; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I