Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Association of Androgen Receptor Gene Polymorphism with Damage in Systemic Lupus Erythematosus.
Deng1, Yun, Grossman2, Jennifer M., Fu1, Qiong, Martin1, William, Quirk1, Matthew, Rullo3, Ornella J., Boackle4, Susan A.
David Geffen School of Medicine University of California Los Angeles, Los Angeles, CA
UCLA David Geffen School of Medicine, Los Angeles, CA
Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, CA
University of Colorado Denver School of Medicine, Aurora, CO
Albert Einstein College of Medicine, Bronx, NY
Hospital for Special Surgery, Weill Cornell Medical College, New York, NY
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
7Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital and The Ohio State University, Columbus, OH
Background/Purpose:
Organ damage predicts physical function and mortality of SLE. The exploration of genes contributing to risk for damage in SLE has been limited. Since men with SLE tend to accrue damage more rapidly, we investigated whether an X-linked androgen receptor (AR) polyGLN polymorphism that impacts androgen receptor transactivation activity correlated with damage assessed by the SLICC/ACR Damage Index (SDI) in SLE.
Methods:
A retrospective chart review was performed to collect the clinical data. The damage score was calculated using SDI, a standardized, validated damage instrument. Length of CAG repeat in exon 1 of AR genotyped by PCR was assessed for association with SDI using the Spearman correlation test, Chi square test, and logistic regression analysis.
Results:
Men with SLE (n = 129) had a shorter disease duration than 422 women with SLE (median [interquartile range]= 5.5 [2–11] vs. 8.5 [3–16] years, p= 0.007), but similar composition of ancestry background, age at onset and cumulative prednisone dose. The proportion of patients who had accrued any damage was higher among men than women in the first 5 years of disease (63.5% vs.39.5%, p= 0.004). Both genders had similar damage accrual in the general SDI categories, except for the renal and pulmonary system in which men were more likely to accrue damage (p= 0.0002 and 0.01, respectively). For AR analysis, CAG repeat length ranged from 12 to 31 in men and 11 to 26 in women with SLE. Combined both genders, the number of CAG repeats varied with ethnicity that the interquartile range was 17–21 in European or Hispanic, 16–19.5 in African, and 18.5–22 in Asian ancestry (p < 0.0001). The lowest quartile of CAG repeat length (n <= 17) was significantly associated with more damage (SDI >=2) in women (OR = 2.49 [1.57–3.94], p= 0.0001), but only in men within the top quartile of disease duration (>16 years) (OR = 3.71 [1.10–12.56], p= 0.04). Using logistic regression analysis, independent risk factors for increased damage (SDI >= 2) in the combined 551 SLE patients were short CAG repeat length (n <= 17) (OR = 2.17 [1.36–3.47], p= 0.001), higher cumulative prednisone dosage (OR = 2.13 [1.62–2.79], p<0.0001), and longer disease duration (OR = 1.06 [1.04–1.09], p<0.0001), but not male gender, non-European ancestry and age at onset which were previously observed to be associated with more organ damage (Table 1).
Table 1. Independent risk factors for increased damage (SDI>=2) in SLE
Conclusion:
Compared to women, men with SLE in this study had accelerated damage accrual particularly in the early course of disease and a higher risk of developing renal and pulmonary damage. The short CAG repeat (<=17), which confers an enhanced androgen transactivation activity resulting in a heightened response of testosterone and DHEA binding might be a prognostic marker for SLE damage in both genders, particularly during the second decade after disease onset. These data support a potential role for androgen signaling in the development of damage in SLE.
To cite this abstract, please use the following information:
Deng, Yun, Grossman, Jennifer M., Fu, Qiong, Martin, William, Quirk, Matthew, Rullo, Ornella J., et al; Association of Androgen Receptor Gene Polymorphism with Damage in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :640
DOI:
