TY - JOUR
T1 - Apolipoprotein H promoter polymorphisms in relation to lupus and lupus-related phenotypes
AU - Suresh, Sangita
AU - Demirci, F. Yesim K.
AU - Jacobs, Erin
AU - Kao, Amy H.
AU - Rhew, Elisa Y.
AU - Sanghera, Dharambir K.
AU - Selzer, Faith
AU - Sutton-Tyrrell, Kim
AU - McPherson, David
AU - Bontempo, Franklin A.
AU - Kammerer, Candace M.
AU - Ramsey-Goldman, Rosalind
AU - Manzi, Susan
AU - Kamboh, M. Ilyas
PY - 2009/2
Y1 - 2009/2
N2 - 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
AB - 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
KW - Apolipoprotein H
KW - Lupus
KW - Polymorphism
KW - Promoter
KW - Systemic lupus erythematosus
KW - β-glycoprotein I
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U2 - 10.3899/jrheum.080482
DO - 10.3899/jrheum.080482
M3 - Article
C2 - 19132787
AN - SCOPUS:64849097573
SN - 0315-162X
VL - 36
SP - 315
EP - 322
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 2
ER -
