TY - JOUR T1 - The Autoimmune Disease Risk Allele of UBE2L3 in African American Patients with Systemic Lupus Erythematosus: A Recessive Effect Upon Subphenotypes JF - The Journal of Rheumatology JO - J Rheumatol SP - 73 LP - 78 DO - 10.3899/jrheum.110590 VL - 39 IS - 1 AU - SANDRA AGIK AU - BEVERLY S. FRANEK AU - AKAASH A. KUMAR AU - MARISSA KUMABE AU - TAMMY O. UTSET AU - RACHEL A. MIKOLAITIS AU - MEENAKSHI JOLLY AU - TIMOTHY B. NIEWOLD Y1 - 2012/01/01 UR - http://www.jrheum.org/content/39/1/73.abstract N2 - 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. Conclusion. 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. ER -