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Endocr Connect. 2014 May 6;3(2):99-109. doi: 10.1530/EC-14-0039. Print 2014.

Variation in the androgen receptor gene exon 1 CAG repeat correlates with manifestations of autoimmunity in women with lupus.

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  • 1Division of Rheumatology Division of EndocrinologyDiabetes, and Metabolism, College of Medicine, Milton S Hershey Medical Center, The Pennsylvania State University, Mail Code H044, 500 University Drive, Hershey, Pennsylvania 17033-0850, USA.

Abstract

Clinical and experimental evidence support a role for gonadal steroids in modulating the expression and course of autoimmune diseases such as lupus. Whether or not inherited variation in sensitivity to circulating androgenic hormones could influence the manifestations of such disease is, however, unknown. We sought to determine whether differences in androgen sensitivity conferred by variation in the exon 1 CAG repeat region of the androgen receptor (AR) gene were associated with differences in the clinical or humoral immune manifestations of lupus in a cohort of female subjects. We found that shorter AR CAG repeat lengths in lupus subjects correlated with a higher Systemic Lupus Erythematosus Disease Activity Index score, higher ANA levels, and expression of a broader array of IgG autoantibodies. Our findings of more severe clinical manifestations and more exuberant humoral autoimmunity in women with a shorter AR exon 1 CAG repeat length suggest a role for genetically determined sensitivity to androgens as a modulator of autoimmune processes.

KEYWORDS:

androgen receptor; humoral autoimmunity; lupus

PMID:
24711544
[PubMed]
PMCID:
PMC4012646
Free PMC Article
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