Estrogen receptor alpha gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women.
OBJECTIVE
Genetic influences have been shown to play an important role in the etiology of osteoarthritis (OA), but the genes involved are ill-defined. We studied the association between polymorphisms in the estrogen receptor alpha (ERalpha) gene and the prevalence of radiographic OA of the knee.


METHODS
The study group comprised 1,483 men and women from the Rotterdam Study. Direct molecular haplotyping was used to determine the relationship between 2 polymorphisms in the ERalpha gene (the Pvu II and Xba I restriction fragment-length polymorphisms). Radiographs of the knee were evaluated according to the Kellgren/Lawrence (K/L) score, along with separate scores for osteophytosis and joint space narrowing.


RESULTS
Three different haplotype alleles were identified: px (54%), PX (34%), and Px (12%). Allele PX was associated with an increased prevalence of radiographic knee OA (K/L score >/=2). The prevalence of radiographic OA was 22% among subjects without allele PX, 24% among those carrying 1 copy, and 35% among subjects carrying 2 copies. The corresponding odds ratios, after adjustment for confounding factors, were 1.3 (95% confidence interval [95% CI] 0.9-1.7) for heterozygotes and 2.2 (95% CI 1.5-3.4) for homozygotes. Separate analyses for men and women showed similar risk estimates. The association appeared to be driven by osteophytosis and is somewhat consistent with the association observed in previous studies of these polymorphisms in relation to OA.


CONCLUSIONS
This study shows that polymorphisms in the ERalpha gene are associated with radiographic OA of the knee, and in particular with osteophytosis, in both elderly men and elderly women.
Bergink
Arjan P
AP
Erasmus University Medical Center, Rotterdam, The Netherlands.
van Meurs
Joyce B
JB
Loughlin
John
J
Arp
Pascal P
PP
Fang
Yue
Y
Hofman
Albert
A
van Leeuwen
Johannes P T M
JP
van Duijn
Cornelia M
CM
Uitterlinden
André G
AG
Pols
Huibert A P
HA
D017677:Age Distribution; D000368:Aged; D047628:Estrogen Receptor alpha; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D011446:Prospective Studies; D011859:Radiography; D011960:Receptors, Estrogen / Q000235:genetics*; D012307:Risk Factors
D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen