RT Journal Article
SR Electronic
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
FD The Journal of Rheumatology
SP 73
OP 78
DO 10.3899/jrheum.110590
VO 39
IS 1
A1 SANDRA AGIK
A1 BEVERLY S. FRANEK
A1 AKAASH A. KUMAR
A1 MARISSA KUMABE
A1 TAMMY O. UTSET
A1 RACHEL A. MIKOLAITIS
A1 MEENAKSHI JOLLY
A1 TIMOTHY B. NIEWOLD
YR 2012
UL http://www.jrheum.org/content/39/1/73.abstract
AB 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.