J Korean Rheum Assoc.  2009 Jun;16(2):115-122. 10.4078/jkra.2009.16.2.115.

Osteopontin Genetic Polymorphism and Serum Levels in Patients with Systemic Lupus Erythematosus

Affiliations
  • 1Department of Laboratory Medicine, Chung-Ang University, College of Medicine, Seoul, Korea. hyekim@cau.ac.kr
  • 2Department of Rheumatology, Chung-Ang University, College of Medicine, Seoul, Korea.

Abstract


OBJECTIVE
A recent study suggested that a single nucleotide polymorphism (SNP) at position nt 9250 (C to T) in exon 7 of the osteopontin (OPN) gene is strongly associated with the susceptibility to systemic lupus erythematosus (SLE). This study examined the possible association between a single nucleotide polymorphism (SNP) at position nt 9250 (C to T) and SLE and measured the serum levels of OPN in Korean patients with SLE.
METHODS
A total of 39 patients with SLE and 104 healthy controls were enrolled in this study. SNP located at position 9250 in the OPN gene were genotyped using the restriction fragment length polymorphism (RFLP). The serum levels of OPN in 39 patients with SLE and 20 healthy controls were determined by enzyme-linked immunosorbent assay.
RESULTS
The allele frequencies of C and T at this position in patients with SLE were 34.6 and 65.4, whereas those in the controls were 20.7 and 79.3 (p<0.05). The serum levels of OPN in 39 patients with SLE were significantly higher than that in 20 healthy controls (49.13+/-26.71 versus 28.49+/-18.39 ng/ml, p<0.05). The increase in OPN concentration was associated with the SLE disease activity index (SLEDAI) score in all SLE patients (r=0.337, p<0.05).
CONCLUSION
The allele frequencies of Eta-1/osteopontin were significantly associated with SLE. Moreover, the increased serum level of OPN is associated with the SLE disease activity. However, further investigation in larger groups in Korea will be needed.

Keyword

Eta-1/osteopontin polymorphism; Serum osteopontin level; Systemic lupus erythematosus

MeSH Terms

Enzyme-Linked Immunosorbent Assay
Exons
Gene Frequency
Humans
Korea
Lupus Erythematosus, Systemic
Osteopontin
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide
Osteopontin

Figure

  • Fig. 1. Representative agarose gel electrophoresis illustrating polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) products for the Eta-1/osteopontin gene polymorphism. The nt 9250 polymorphism in exon 7: lane 1, homozygous C/C subject; lane 2, heterozygous C/T subject; lane3, homozygous T/T subject. C allele cut with Alu I generating 147- and 105-bp fragments and T allele cut with Alu I generating 61- and 44-bp fragments.

  • Fig. 2. Correlation between serum osteopontin (OPN) level and systemic lupus erythematosus disease activity index (SLEDAI).


Reference

References

1. Weber GF, Cantor H. The immunology of Eta-1/osteopontin. Cytokine Growth Factor Rev. 1996; 7:241–8.
Article
2. Stromnes IM, Goveman JM. Osteopontin-induced survival of T cells. Nat Immunol. 2007; 8:19–20.
Article
3. Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, et al. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science. 2000; 287:860–4.
Article
4. O'Regan AW, Hayden JM, Berman JS. Osteopontin augments CD3-mediated interferon-gamma and CD40 ligand expression by T cells, which results in IL-12 prodution from peripheral blood mononuclear cells. J Leukoc Biol. 2000; 68:495–502.
5. Forton AC, Petri MA, Goldman D, Sullivan KE. An osteopontin (SPP1) polymorphism is associated with systemic lupus erythematosus. Hum Mutat. 2002; 19:459–62.
Article
6. Xu AP, Bai J, LüJ , Liang YY, Li JG, Lai DY, et al. Osteopontin gene polymorphism in association with systemic lupus erythematosus in Chinese patients. Chin Med J. 2007; 120:2124–8.
Article
7. D'Alfonso S, Barizzone N, Giordano M, Chiocchetti A, Magnani C, Castelli L, et al. Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus. Arthritis Rheum. 2005; 52:539–47.
8. Bautista DS, Xuan JW, Hota C, Chambers AF, Harris JF. Inhibition of Arg-Gly-Asp (RGD)-mediated cell adhesion to osteopontin by a monoclonal antibody against osteopontin. J Biol Chem. 1994; 269:23280–5.
Article
9. Qin LX, Tang ZY. Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature. J Cancer Res Clin Oncol. 2004; 130:497–513.
Article
10. Vogt MH, Lopatinskaya L, Smits M, Polman CH, Nagelkerken L. Elevated osteopontin levels in active relapsing-remitting multiple sclerosis. Ann Neurol. 2003; 53:819–22.
Article
11. Chiocchetti A, Indelicato M, Bensi T, Mesturini R, Giordano M, Sametti S, et al. High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lym-phoproliferation. Blood. 2004; 103:1376–82.
Article
12. Masutani K, Akahoshi M, Tsuruya K, Tokumoto M, Ninomiya T, Kohsaka T, et al. Predominance of Th1 immune response in diffuse proliferative lupus nephritis. Arthritis Rheum. 2001; 44:2097–106.
Article
13. Wong CK, Lit LC, Tam LS, Li EK, Lam CW. Elevation of plasma osteopontin concentration is correlated with disease activity in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2005; 44:602–6.
Article
14. O'Regan AW, Nau GJ, Chupp GL, Berman JS. Osteopontin (Eta-1) in cell-mediated immunity: teaching an old dog new tricks. Immunol Today. 2000; 21:475–8.
15. Xie Y, Sakatsume M, Nishi S, Narita I, Arakawa M, Gejyo F. Expression, roles, receptors, and regulation of osteopontin in the kidney. Kidney Int. 2001; 60:1645–57.
Article
16. Iwasaki H, Shinohara Y, Ezura Y, Ishida R, Kodaira M, Kajita M, et al. Thirteen single-nucleotide polymorphisms in the human osteopontin gene identified by sequencing of the entire gene in Japanese individuals. J Hum Genet. 2001; 46:544–6.
Article
17. Iizuka J, Katagiri Y, Tada N, Murakami M, Ikeda T, Sato M, et al. Introduction of an osteopontin gene confers the increase in B1 cell population and the production of anti-DNA autoantibodies. Lab Invest. 1998; 78:1523–33.
18. Ophascharoensuk V, Giachelli CM, Gordon K, Hughes J, Pichler R, Brown P, et al. Obstructive uropathy in the mouse: role of osteopontin in interstitial fibrosis and apoptosis. Kidney Int. 1999; 56:571–80.
Article
19. Niino M, Kikuchi S, Fukazawa T, Yabe I, Tashiro K. Genetic polymorphisms of osteopontin in association with multiple sclerosis in Japanese patients. J Neuroimmunol. 2003; 136:125–9.
Article
20. Tsao BP, Grossman JM. Genetics and systemic lupus erythematosus. Curr Rheumatol Rep. 2001; 3:183–90.
Article
Full Text Links
  • JKRA
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr