The relationship of estrogen receptor-alpha and -beta genes with osteoarthritis of the hand.
OBJECTIVE
We examined reported associations between radiographic hand osteoarthritis (OA) and single-nucleotide polymorphisms (SNP) in 2 candidate genes associated with OA in other joints: estrogen receptor alpha (ESR1) and beta (ESR2).


METHODS
In 539 Framingham Offspring Study participants (49% men; mean age 61 +/- 9 yrs) joint-specific radiographic hand OA was defined as Kellgren/Lawrence (K/L) scores >or= 2 in the first carpometacarpal joint (CMC), distal interphalangeal joints (DIP), first-digit interphalangeal joint (IP), or proximal interphalangeal joints (PIP). Four SNP were genotyped for ESR1 (PvuII-rs2234693, XbaI-rs9340799, rs2077647, and rs1801132) and 4 for ESR2 (rs1256031, rs1256034, rs1256059, rs944460). Logistic regression analyses were performed to evaluate the relationships between genotypes and hand OA, adjusting for age, sex, height, and weight.


RESULTS
Radiographic hand OA was identified in at least one investigated joint of DIP (39%), PIP (33%), and first CMC (40%). There was no evidence of association between OA and genotype at any polymorphism. We found no significant association between our OA phenotypes or generalized or severe generalized OA as defined by Ushiyama and heterozygosity for rs2234693 and rs9340799, although in metaanalysis with the former study this heterozygosity remained significantly associated with generalized or severe generalized OA.


CONCLUSIONS
We found no significant association between hand OA and the investigated polymorphisms of ESR1 or ESR2 despite published reports of association and a priori hypotheses implicating their potential roles. However, we could not absolutely exclude associations with rs2234693, rs9340799, or rs944460.
Wise
Barton L
BL
Framingham Heart Study, National Heart, Lung and Blood Institute, National Institutes of Health, Boston, Massachusetts, USA.
Demissie
Serkalem
S
Cupples
L Adrienne
LA
Felson
David T
DT
Yang
Mei
M
Shearman
Amanda M
AM
Aliabadi
Piran
P
Hunter
David J
DJ
D000368:Aged; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006225:Hand / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011859:Radiography
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta