title: Apolipoprotein H promoter polymorphisms in relation to lupus and lupus-related phenotypes.
abstract: 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 ss(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 ~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).
  
  
  CONCLUSIONS
  Our data indicate that APOH promoter variants may be involved in the etiology of SLE, especially the risk for autoimmune-mediated cardiovascular disease.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, A300 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA 15261, USA.
authors.forename: Sangita
authors.initials: S
authors.lastname: Suresh
authors.forename: F Yesim K
authors.initials: FY
authors.lastname: Demirci
authors.forename: Erin
authors.initials: E
authors.lastname: Jacobs
authors.forename: Amy H
authors.initials: AH
authors.lastname: Kao
authors.forename: Elisa Y
authors.initials: EY
authors.lastname: Rhew
authors.forename: Dharambir K
authors.initials: DK
authors.lastname: Sanghera
authors.forename: Faith
authors.initials: F
authors.lastname: Selzer
authors.forename: Kim
authors.initials: K
authors.lastname: Sutton-Tyrrell
authors.forename: David
authors.initials: D
authors.lastname: McPherson
authors.forename: Franklin A
authors.initials: FA
authors.lastname: Bontempo
authors.forename: Candace M
authors.initials: CM
authors.lastname: Kammerer
authors.forename: Rosalind
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.forename: Susan
authors.initials: S
authors.lastname: Manzi
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D000328:Adult; D001665:Binding Sites / Q000235:genetics; D016893:Carotid Stenosis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D004252:DNA Mutational Analysis; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008181:Lupus Nephritis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D053482:beta 2-Glycoprotein I / Q000235:genetics*
chemical_list: D053482:beta 2-Glycoprotein I