Apolipoprotein H promoter polymorphisms in relation to lupus and lupus-related phenotypes

Sangita Suresh, F. Yesim K. Demirci, Erin Jacobs, Amy H. Kao, Elisa Y. Rhew, Dharambir K. Sanghera, Faith Selzer, Kim Sutton-Tyrrell, David McPherson, Franklin A. Bontempo, Candace M. Kammerer, Rosalind Ramsey-Goldman, Susan Manzi, M. Ilyas Kamboh

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Objective. Sequence variation in gene promoters is often associatedwith disease risk.We tested the hypothesis that common promoter variation in theAPOH gene (encoding for β2-glycoprotein I) is associated with systemic lupus erythematosus (SLE) risk and SLE-related clinical phenotypes in a Caucasian cohort. Methods. We used a case-control design and genotyped 345 women with SLE and 454 healthy control women for 8 APOH promoter single-nucleotide polymorphisms (SNP; -1284C>G, -1219G>A, -1190G>C, -759A>G, -700C>A, -643T>C, -38G>A, and -32C>A).Association analyses were performed on single SNP and haplotypes. Haplotype analyses were performed using EH (Estimate Haplotype-frequencies) and Haploview programs. In vitro reporter gene assay was performed in COS-1 cells. Electrophoretic mobility shift assay (EMSA) was performed using HepG2 nuclear cells. Results. Overall haplotype distribution of the APOH promoter SNP was significantly different between cases and controls (p = 0.009). The -643C allele was found to be protective against carotid plaque formation (adjusted OR 0.37, p = 0.013) among patients with SLE. The -643C allele was associated with a ∼2-fold decrease in promoter activity as compared to wild-type -643T allele (mean ± standard deviation: 3.94 ± 0.05 vs 6.99 ± 0.68, p = 0.016). EMSA showed that the -643T>C SNP harbors a binding site for a nuclear factor. The -1219G>A SNP showed a significant association with the risk of lupus nephritis (age-adjusted OR 0.36, p = 0.016). Conclusion. Our data indicate that APOH promoter variants may be involved in the etiology of SLE, especially the risk for autoimmune-mediated cardiovascular disease. The Journal of Rheumatology

Original languageEnglish (US)
Pages (from-to)315-322
Number of pages8
JournalJournal of Rheumatology
Issue number2
StatePublished - Feb 2009


  • Apolipoprotein H
  • Lupus
  • Polymorphism
  • Promoter
  • Systemic lupus erythematosus
  • β-glycoprotein I

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology


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