A prospective study of androgen levels, hormone-related genes and risk of rheumatoid arthritis.
BACKGROUND
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.
Karlson
Elizabeth W
EW
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. ekarlson@partners.org
Chibnik
Lori B
LB
McGrath
Monica
M
Chang
Shun-Chiao
SC
Keenan
Brendan T
BT
Costenbader
Karen H
KH
Fraser
Patricia A
PA
Tworoger
Shelley
S
Hankinson
Susan E
SE
Lee
I-Min
IM
Buring
Julie
J
De Vivo
Immaculata
I
D000328:Adult; D000368:Aged; D000728:Androgens / Q000097:blood* / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D011944:Receptors, Androgen / Q000097:blood / Q000235:genetics; D012307:Risk Factors
D000728:Androgens; D011944:Receptors, Androgen