TY - JOUR
T1 - A prospective study of androgen levels, hormone-related genes and risk of rheumatoid arthritis
AU - Karlson, Elizabeth W.
AU - Chibnik, Lori B.
AU - McGrath, Monica
AU - Chang, Shun Chiao
AU - Keenan, Brendan T.
AU - Costenbader, Karen H.
AU - Fraser, Patricia A.
AU - Tworoger, Shelley
AU - Hankinson, Susan E.
AU - Lee, I. Min
AU - Buring, Julie
AU - De Vivo, Immaculata
N1 - Funding Information:
The authors thank the participants in the NHS and the WHS cohorts for their dedication and continued participation in these longitudinal studies, and thank the staff of the NHS and WHS for their assistance with this project. The present work was supported by NIH grants R01 AR49880, CA87969, HL43851, HL 080467 CA47988, P60 AR047782, K24 AR0524-01 and BIRCWH K12 HD051959 (supported by NIMH, NIAID, NICHD, and OD). KHC is the recipient of an Arthritis Foundation/American College of Rheumatology Arthritis Investigator Award and a Katherine Swan Ginsburg Memorial Award.
PY - 2009/6/25
Y1 - 2009/6/25
N2 - Introduction: Rheumatoid arthritis (RA) is more common in females than males and sex steroid hormones may in part explain this difference. We conducted a case-control study nested within two prospective studies to determine the associations between plasma steroid hormones measured prior to RA onset and polymorphisms in the androgen receptor (AR), estrogen receptor 2 (ESR2), aromatase (CYP19) and progesterone receptor (PGR) genes and RA risk. Methods: We genotyped AR, ESR2, CYP19, PGR SNPs and the AR CAG repeat in RA case-control studies nested within the Nurses' Health Study (NHS), NHS II (449 RA cases, 449 controls) and the Women's Health Study (72 cases, and 202 controls). All controls were matched on cohort, age, Caucasian race, menopausal status, and postmenopausal hormone use. We measured plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone binding globulin in 132 pre-RA samples and 396 matched controls in the NHS cohorts. We used conditional logistic regression models adjusted for potential confounders to assess RA risk. Results: Mean age of RA diagnosis was 55 years in both cohorts; 58% of cases were rheumatoid factor positive at diagnosis. There was no significant association between plasma DHEAS, total testosterone, or calculated free testosterone and risk of future RA. There was no association between individual variants or haplotypes in any of the genes and RA or seropositive RA, nor any association for the AR CAG repeat. Conclusions: Steroid hormone levels measured at a single time point prior to RA onset were not associated with RA risk in this study. Our findings do not suggest that androgens or the AR, ESR2, PGR, and CYP19 genes are important to RA risk in women.
AB - Introduction: Rheumatoid arthritis (RA) is more common in females than males and sex steroid hormones may in part explain this difference. We conducted a case-control study nested within two prospective studies to determine the associations between plasma steroid hormones measured prior to RA onset and polymorphisms in the androgen receptor (AR), estrogen receptor 2 (ESR2), aromatase (CYP19) and progesterone receptor (PGR) genes and RA risk. Methods: We genotyped AR, ESR2, CYP19, PGR SNPs and the AR CAG repeat in RA case-control studies nested within the Nurses' Health Study (NHS), NHS II (449 RA cases, 449 controls) and the Women's Health Study (72 cases, and 202 controls). All controls were matched on cohort, age, Caucasian race, menopausal status, and postmenopausal hormone use. We measured plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone binding globulin in 132 pre-RA samples and 396 matched controls in the NHS cohorts. We used conditional logistic regression models adjusted for potential confounders to assess RA risk. Results: Mean age of RA diagnosis was 55 years in both cohorts; 58% of cases were rheumatoid factor positive at diagnosis. There was no significant association between plasma DHEAS, total testosterone, or calculated free testosterone and risk of future RA. There was no association between individual variants or haplotypes in any of the genes and RA or seropositive RA, nor any association for the AR CAG repeat. Conclusions: Steroid hormone levels measured at a single time point prior to RA onset were not associated with RA risk in this study. Our findings do not suggest that androgens or the AR, ESR2, PGR, and CYP19 genes are important to RA risk in women.
UR - http://www.scopus.com/inward/record.url?scp=67650666445&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67650666445&partnerID=8YFLogxK
U2 - 10.1186/ar2742
DO - 10.1186/ar2742
M3 - Article
C2 - 19555469
AN - SCOPUS:67650666445
SN - 1478-6354
VL - 11
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 3
M1 - R97
ER -