title: Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus.
abstract: OBJECTIVE
  To test the association of osteopontin (OPN) polymorphisms with systemic lupus erythematosus (SLE).
  
  
  METHODS
  The coding 5' and 3' flanking regions of the OPN gene were scanned for polymorphisms by denaturing high-performance liquid chromatography. A case-control association study was performed in 394 Italian SLE patients and 479 matched controls. OPN serum levels were determined by enzyme-linked immunosorbent assay in 40 patients and 124 controls, and the mean levels were compared between the different OPN genotypes.
  
  
  RESULTS
  Among the 13 detected single-nucleotide polymorphisms (SNPs), alleles -156G (frequency 0.714 versus 0.651; P = 0.006, corrected P [P(corr)] = 0.036) and +1239C (0.377 versus 0.297; P = 0.00094, P(corr) = 0.0056) were significantly increased in the SLE patients compared with the controls. The presence of the associated allele in single or double dose conferred an odds ratio (OR) of 2.35 (95% confidence interval [95% CI] 1.38-4.02) for SNP -156 and an OR of 1.57 (95% CI 1.16-2.13) for SNP +1239. These effects were independent of each other, i.e., not a consequence of linkage disequilibrium between the 2 alleles. The risk associated with a double dose of susceptibility alleles at both SNPs was 3.8-fold higher (95% CI 2.0-7.4) relative to the complete absence of susceptibility alleles. With regard to individual clinical and immunologic features, a significant association was seen between lymphadenopathy and -156 genotypes (overall P = 0.0011, P(corr) = 0.046). A significantly increased OPN serum level was detected in healthy individuals carrying +1239C (P = 0.002), which is indicative of an association between the SLE susceptibility allele and OPN levels.
  
  
  CONCLUSIONS
  These data suggest the independent effect of a promoter (-156) and a 3'-untranslated region (+1239) SNP in SLE susceptibility. We can speculate that these sequence variants (or others in perfect linkage disequilibrium) create a predisposition to high production of OPN, and that this in turn may confer susceptibility to SLE.
authors.affiliation: Department of Medical Sciences and IRCAD, University of Eastern Piedmont, Novara, Italy. dalfonso@med.unipmn.it <dalfonso@med.unipmn.it>
authors.forename: S
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: N
authors.initials: N
authors.lastname: Barizzone
authors.forename: M
authors.initials: M
authors.lastname: Giordano
authors.forename: A
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: C
authors.initials: C
authors.lastname: Magnani
authors.forename: L
authors.initials: L
authors.lastname: Castelli
authors.forename: M
authors.initials: M
authors.lastname: Indelicato
authors.forename: F
authors.initials: F
authors.lastname: Giacopelli
authors.forename: M
authors.initials: M
authors.lastname: Marchini
authors.forename: R
authors.initials: R
authors.lastname: Scorza
authors.forename: M G
authors.initials: MG
authors.lastname: Danieli
authors.forename: M
authors.initials: M
authors.lastname: Cappelli
authors.forename: S
authors.initials: S
authors.lastname: Migliaresi
authors.forename: B
authors.initials: B
authors.lastname: Bigliardo
authors.forename: M G
authors.initials: MG
authors.lastname: Sabbadini
authors.forename: E
authors.initials: E
authors.lastname: Baldissera
authors.forename: M
authors.initials: M
authors.lastname: Galeazzi
authors.forename: G D
authors.initials: GD
authors.lastname: Sebastiani
authors.forename: G
authors.initials: G
authors.lastname: Minisola
authors.forename: R
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: U
authors.initials: U
authors.lastname: Dianzani
authors.forename: P
authors.initials: P
authors.lastname: Momigliano-Richiardi
mesh_terms: D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D053495:Osteopontin; D020641:Polymorphism, Single Nucleotide; D012795:Sialoglycoproteins / Q000097:blood / Q000235:genetics*
chemical_list: C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin