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-αsubgroup (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. The Journal of Rheumatology
Original language | English (US) |
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Pages (from-to) | 73-78 |
Number of pages | 6 |
Journal | Journal of Rheumatology |
Volume | 39 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2012 |
Keywords
- Autoantibodies
- Genetics
- Interferon-α
- Systemic lupus erythematosus
- UBE2L3 genotype
ASJC Scopus subject areas
- Rheumatology
- Immunology and Allergy
- Immunology