SPP1 – Systemic Lupus Erythematosus

Common variants in the osteopontin gene (SPP1) have been associated with systemic lupus erythematosus (SLE) susceptibility and specific clinical features in multiple cohort studies. In 265 SLE patients, the 3′UTR risk allele rs9138C conferred higher serum OPN and IFN-α in men (P=0.0062, P=0.0087) and in younger women (P<0.0001), with distinct promoter SNPs rs11730582 and rs28357094 linked to anti-RNP antibodies in African-Americans (OR=2.9, OR=3.9) (PMID:19339987). In a multiethnic cohort of 252 SLE patients, rs9138C was associated with photosensitivity (meta-analysis OR=3.2) (PMID:22131818), while rs11730582C showed suggestive associations with thrombocytopenia (OR=2.1) and hemolytic anemia (OR=2.6) (PMID:22131818).

Functional correlations demonstrate that SPP1 risk alleles modulate serum osteopontin levels and downstream IFN-α production, linking genotype to the IFN pathway in SLE. These findings support a multifactorial mechanism in which SPP1 variants act as moderate-effect susceptibility alleles without clear Mendelian segregation or high-penetrance loss-of-function mutations. No conflicting or refuting reports have been identified to date. Key take-home: SPP1 risk variants influence IFN-α signaling and clinical manifestations in SLE, offering potential biomarkers for stratification and novel therapeutic targeting.

References

• Genes and immunity • 2009 • Age- and gender-specific modulation of serum osteopontin and interferon-alpha by osteopontin genotype in systemic lupus erythematosus. PMID:19339987
• Journal of biomedicine & biotechnology • 2011 • Osteopontin alleles are associated with clinical characteristics in systemic lupus erythematosus. PMID:22131818

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