Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women.
OBJECTIVE
This study evaluated the association between polymorphisms in the estrogen receptor (ER) alpha gene (ESR1) and prevalent and incident radiographic hip osteoarthritis (RHOA) in a large, well-defined prospective cohort of elderly Caucasian women.


METHODS
Prevalent and incident RHOA was evaluated from all available pelvis X-rays obtained from the Study of Osteoporotic Fractures at baseline and after a mean of 8.3 years. Evaluable DNA samples were available from 4746 of these subjects. RHOA cases were defined by published methods. The ESR1 polymorphisms at intron I (Pvu II for a T/C substitution and Xba I for an A/G substitution) were genotyped in the context of a multiplex polymerase chain reaction (PCR) amplification followed by allele-specific single nucleotide polymorphism (SNP) detection with immobilized oligonucleotide probes in linear arrays. Multiple logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) associated with the T/C and A/G polymorphisms.


RESULTS
RHOA was present in 12.1% of subjects, of whom 325 had joint space narrowing (JSN) score > or =3 and 130 had an osteophyte score > or =2 and JSN score > or =2. There was a significant reduction in the odds of prevalent RHOA for individuals with the C/C compared to T/T genotype at the Pvu II site with an OR of 0.71 (95% CI: 0.55-0.92) (P=0.01). Adjustments for age, weight, height, hip Bone mineral density (BMD) and estrogen use did not alter the relationship between the C/C genotype and reduced risk of RHOA, with an OR of 0.71 (95% CI: 0.54-0.94) (P=0.01). The risk of incident RHOA was reduced for the Pvu II C/C compared to the T/T genotype (P=0.11). Also, the reduced risk of incident RHOA in C/C subjects varied by estrogen use. There was no association between the Xba I G/G or G/A genotypes and RHOA with OR of 0.82 (95% CI: 0.61-1.10) (P=0.19) compared to women with A/A genotype.


CONCLUSIONS
We conclude that the C/C genotype of the ER alpha Pvu II polymorphism was associated with a modestly reduced risk of prevalent and incident RHOA in elderly Caucasian women. Additional work is required to understand how the intron I ESR1 polymorphism may alter joint degeneration.
Lian
K
K
Department of Epidemiology, University of California at San Francisco, San Francisco, CA 94143, USA.
Lui
L
L
Zmuda
J M
JM
Nevitt
M C
MC
Hochberg
M C
MC
Lee
J M
JM
Li
J
J
Lane
N E
NE
D000368:Aged; D000369:Aged, 80 and over; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006620:Hip Fractures / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics; D006801:Humans; D015994:Incidence; D007438:Introns / Q000235:genetics; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging / Q000208:ethnology* / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D011446:Prospective Studies; D011859:Radiography; D044465:White People / Q000706:statistics & numerical data*
D047628:Estrogen Receptor alpha