PT  - JOURNAL ARTICLE
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
TI  - The Autoimmune Disease Risk Allele of UBE2L3 in African American Patients with Systemic Lupus Erythematosus: A Recessive Effect Upon Subphenotypes
AID  - 10.3899/jrheum.110590
DP  - 2011 Nov 01
TA  - The Journal of Rheumatology
PG  - jrheum.110590
4099  - http://www.jrheum.org/content/early/2011/10/28/jrheum.110590.short
4100  - http://www.jrheum.org/content/early/2011/10/28/jrheum.110590.full
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.