title: The autoimmune disease risk allele of UBE2L3 in African American patients with systemic lupus erythematosus: a recessive effect upon subphenotypes.
abstract: OBJECTIVE
  UBE2L3 is associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis in European ancestry populations, and this locus has not been investigated fully in non-European populations. We studied the UBE2L3 risk allele for association with SLE, interferon-α (IFN-α), and autoantibodies in a predominantly African American SLE cohort.
  
  
  METHODS
  We studied 395 patients with SLE and 344 controls. The UBE2L3 rs5754217 polymorphism was genotyped using Taqman primer-probe sets, and IFN-α was measured using a reporter cell assay.
  
  
  RESULTS
  The UBE2L3 rs5754217 T allele was strongly enriched in African American patients with anti-La antibodies as compared to controls, and a recessive model was the best fit for this association (OR 2.55, p = 0.0061). Serum IFN-α also demonstrated a recessive association with the rs5754217 genotype in African American patients, and the TT/anti-La-positive patients formed a significantly high IFN-α subgroup (p = 0.0040). Similar nonstatistically significant patterns of association were observed in the European American patients with SLE. Case-control analysis did not show large allele frequency differences, supporting the idea that this allele is most strongly associated with anti-La-positive patients.
  
  
  CONCLUSIONS
  This pattern of recessive influence within a subgroup of patients may explain why this allele does not produce a strong signal in standard case-control studies, and subphenotypes should be included in future studies of UBE2L3. The interaction we observed between UBE2L3 genotype and autoantibodies upon serum IFN-α suggests a biological role for this locus in patients with SLE in vivo.
authors: University of Chicago, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, 924 East 57th Street, R420, Chicago, IL 60637, USA.
authors: Sandra
authors: S
authors: Agik
authors: Beverly S
authors: BS
authors: Franek
authors: Akaash A
authors: AA
authors: Kumar
authors: Marissa
authors: M
authors: Kumabe
authors: Tammy O
authors: TO
authors: Utset
authors: Rachel A
authors: RA
authors: Mikolaitis
authors: Meenakshi
authors: M
authors: Jolly
authors: Timothy B
authors: TB
authors: Niewold
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012261:Ribonucleoproteins / Q000276:immunology; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*; D044465:White People / Q000235:genetics; D000097585:SS-B Antigen
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D016898:Interferon-alpha; D012261:Ribonucleoproteins; D044763:Ubiquitin-Conjugating Enzymes; D000097585:SS-B Antigen; C079437:UBE2L3 protein, human