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Age- and gender-specific modulation of serum osteopontin and interferon-α by osteopontin genotype in systemic lupus erythematosus


Osteopontin (OPN) is a multifunctional cytokine involved in long bone remodeling and immune system signaling. Additionally, OPN is critical for interferon-α (IFN-α) production in murine plasmacytoid dendritic cells. We have previously shown that IFN-α is a heritable risk factor for systemic lupus erythematosus (SLE). Genetic variants of OPN have been associated with SLE susceptibility, and one study suggests that this association is particular to men. In this study, the 3′ UTR SLE-risk variant of OPN (rs9138C) was associated with higher serum OPN and IFN-α in men (P=0.0062 and P=0.0087, respectively). In women, the association between rs9138 C and higher serum OPN and IFN-α was restricted to younger subjects, and risk allele carriers showed a strong age-related genetic effect of rs9138 genotype on both serum OPN and IFN-α (P<0.0001). In African-American subjects, the 5′ region single nucleotide polymorphisms, rs11730582 and rs28357094, were associated with anti-RNP antibodies (odds ratio (OR)=2.9, P=0.0038 and OR=3.9, P=0.021, respectively). Thus, we demonstrate two distinct genetic influences of OPN on serum protein traits in SLE patients, which correspond to previously reported SLE-risk variants. This study provides a biologic relevance for OPN variants at the protein level, and suggests an influence of this gene on the IFN-α pathway in SLE.

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Grant support and disclosures: SN Kariuki – none; JG Moore – none; KA Kirou – patent pending for interferon assay; MK Crow – NIH AI059893, Alliance for Lupus Research, Mary Kirkland Center for Lupus Research, Lupus Research Institute, and patent pending for interferon assay; TO Utset – Lupus Clinical Trials Consortium, Genentech; TB Niewold – NIH CTSA K12 Scholar Award RR025000-02, NIAID Clinical Research Loan Repayment AI071651, Arthritis Foundation Post-Doctoral Fellowship Award, Arthritis National Research Foundation Scholar Award.

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Correspondence to T B Niewold.

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Kariuki, S., Moore, J., Kirou, K. et al. Age- and gender-specific modulation of serum osteopontin and interferon-α by osteopontin genotype in systemic lupus erythematosus. Genes Immun 10, 487–494 (2009).

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  • systemic lupus erythematosus
  • interferon-α
  • osteopontin
  • age
  • gender
  • autoantibodies

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