The autoimmune disease risk allele of UBE2L3 in African American patients with systemic lupus erythematosus: A recessive effect upon subphenotypes

Sandra Agik, Beverly S. Franek, Akaash A. Kumar, Marissa Kumabe, Tammy O. Utset, Rachel A. Mikolaitis, Meenakshi Jolly, Timothy B. Niewold

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)73-78
Number of pages6
JournalJournal of Rheumatology
Volume39
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Fingerprint

African Americans
Systemic Lupus Erythematosus
Autoimmune Diseases
Alleles
Autoantibodies
Genotype
Rheumatology
Serum
Gene Frequency
Interferons
Population
Case-Control Studies
Anti-Idiotypic Antibodies
Rheumatoid Arthritis

Keywords

  • Autoantibodies
  • Genetics
  • Interferon-α
  • Systemic lupus erythematosus
  • UBE2L3 genotype

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

The autoimmune disease risk allele of UBE2L3 in African American patients with systemic lupus erythematosus : A recessive effect upon subphenotypes. / Agik, Sandra; Franek, Beverly S.; Kumar, Akaash A.; Kumabe, Marissa; Utset, Tammy O.; Mikolaitis, Rachel A.; Jolly, Meenakshi; Niewold, Timothy B.

In: Journal of Rheumatology, Vol. 39, No. 1, 01.2012, p. 73-78.

Research output: Contribution to journalArticle

Agik, Sandra ; Franek, Beverly S. ; Kumar, Akaash A. ; Kumabe, Marissa ; Utset, Tammy O. ; Mikolaitis, Rachel A. ; Jolly, Meenakshi ; Niewold, Timothy B. / The autoimmune disease risk allele of UBE2L3 in African American patients with systemic lupus erythematosus : A recessive effect upon subphenotypes. In: Journal of Rheumatology. 2012 ; Vol. 39, No. 1. pp. 73-78.
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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",
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T1 - The autoimmune disease risk allele of UBE2L3 in African American patients with systemic lupus erythematosus

T2 - A recessive effect upon subphenotypes

AU - Agik, Sandra

AU - Franek, Beverly S.

AU - Kumar, Akaash A.

AU - Kumabe, Marissa

AU - Utset, Tammy O.

AU - Mikolaitis, Rachel A.

AU - Jolly, Meenakshi

AU - Niewold, Timothy B.

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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-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

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-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

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KW - Genetics

KW - Interferon-α

KW - Systemic lupus erythematosus

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