title: Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women.
abstract: 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.
authors.affiliation: Department of Epidemiology, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: K
authors.initials: K
authors.lastname: Lian
authors.forename: L
authors.initials: L
authors.lastname: Lui
authors.forename: J M
authors.initials: JM
authors.lastname: Zmuda
authors.forename: M C
authors.initials: MC
authors.lastname: Nevitt
authors.forename: M C
authors.initials: MC
authors.lastname: Hochberg
authors.forename: J M
authors.initials: JM
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: N E
authors.initials: NE
authors.lastname: Lane
mesh_terms: 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*
chemical_list: D047628:Estrogen Receptor alpha