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. . 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. Conclusion. 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.Systemic lupus erythematosus (SLE) is an autoimmune disease with a multifactorial etiology that is characterized by impaired T cell responses and dysregulation of B cell activation, leading to B cell hyperactivity and production of autoantibodies. Several lines of evi-

A Study of the Association of Polymorphism rs5860110 and its Protective Role against Ankylosing Spondylitis in a Chinese Population

“…So far, genetic variants in the SPP1 gene have shown to be involved in susceptibility to other immune-mediated diseases such as SLE [8,9], oligoarticular juvenile idiopathic arthritis [26] and sarcoidosis [27]. Despite promising functional data, previous genotype analyses could not confirm SPP1 as significant disease modifying gene in classical Th17-mediated diseases such as multiple sclerosis [28,29] and rheumatoid arthritis [30].…”

“…SPP1 mainly contributes to host defence, bone formation, and wound healing by stimulating macrophage migration as well as protecting against viral and bacterial infections through its pro-Th1 effect [7]. It has been shown that The SPP1 polymorphisms were associated with susceptibility to systemic lupus erythematosus (SLE) [8][9][10]. In addition, it was associated with many types of cancer, such as nasopharyngeal carcinoma [11], colorectal carcinoma [12], breast cancer [13], non-small-cell lung cancer [14], gastric cancer [15].…”

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

“…In a study of D'Alfonso et al [39], a total of 13 SNPs in OPN gene were identiied (six in the 5' lanking region, one in intron 3, three in exons 6, 7 and three in the 3'-UTR). Two polymorphisms: −156G/GG (rs7687316, in promoter) and +1239A/C (rs9138, in 3′-UTR) were signiicantly associated with SLE.…”

Genetic Polymorphisms of Osteopontin in Association with Ankylosing Spondylitis in a Chinese Population

“…So far, genetic variants in OPN gene have been shown to be involved in susceptibility to other immune-mediated diseases such as SLE [29,30], oligoarticular juvenile idiopathic arthritis [31] and sarcoidosis [32]. Despite promising functional data, previous genotype analyses could not confirm SPP1 as significant disease modifying gene in classical Th17-mediated diseases such as multiple sclerosis [33,34] and rheumatoid arthritis [35].…”