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Estrogen receptor α gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women

✍ Scribed by Arjan P. Bergink; Joyce B. van Meurs; John Loughlin; Pascal P. Arp; Yue Fang; Albert Hofman; Johannes P. T. M. van Leeuwen; Cornelia M. van Duijn; André G. Uitterlinden; Huibert A. P. Pols

Publisher
John Wiley and Sons
Year
2003
Tongue
English
Weight
100 KB
Volume
48
Category
Article
ISSN
0004-3591

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✦ Synopsis

Abstract

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 α (ERα) 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 ERα 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.

Conclusion

This study shows that polymorphisms in the ERα gene are associated with radiographic OA of the knee, and in particular with osteophytosis, in both elderly men and elderly women.

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