Two single‐nucleotide polymorphisms in the 5′ and 3′ ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus

作者：Sandra D’Alfonso, Nadia Barizzone, Mara Giordano, Annalisa Chiocchetti, Corrado Magnani, Luca Castelli, Manuela Indelicato, Francesca Giacopelli, Maurizio Marchini, R Scorza, Maria Giovanna Danieli, M. Cappelli, Sergio Migliaresi, B. Bigliardo, M Grazia Sabbadini, Elena Marina Baldissera, M. Galeazzi, Gian Domenico Sebastiani, Giovanni Minisola, Roberto Ravazzolo, Umberto Dianzani, Patricia Momigliano‐Richiardi · 发表于：Arthritis & Rheumatism · 年份：2005 · DOI：10.1002/art.20808 · 被引用次数：103 · 研究领域：Bone and Dental Protein Studies、dental development and anomalies、Bone Metabolism and Diseases

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(co...