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

• Published in: Genes and immunity Vol. 10; no. 5; pp. 487 - 494
• Main Authors: Kariuki, S N, Moore, J G, Kirou, K A, Crow, M K, Utset, T O, Niewold, T B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-07-2009; Nature Publishing Group
• Subjects: 3' Untranslated regions; Adolescent; Adult; Age; Age Factors; Aged; Biomedical and Life Sciences; Biomedicine; Bone remodeling; Cancer Research; Child; Dendritic cells; Female; Gene Expression; Genetic diversity; Human Genetics; Humans; Immune system; Immunology; Interferon; Interferon-alpha - immunology; Long bone; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - epidemiology; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Male; Middle Aged; original-article; Osteopontin; Osteopontin - blood; Osteopontin - genetics; Risk factors; Sex Factors; Single-nucleotide polymorphism; Systemic lupus erythematosus; Young Adult; α-Interferon; systemic lupus erythematosus; interferon-α; gender; autoantibodies; osteopontin; age
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2009.15

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.