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摘要
Objective. Sequence variation in gene promoters is often associated with disease risk. We tested the hypothesis that common promoter variation in the APOH gene (encoding for beta(2)-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 similar to 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 -12196>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. (First Release Dec 15 2008; J Rheumatol 2009;36:315-22; doi: 10.3899/jrheum.080482)
- 出版日期2009-2
- 单位西北大学
