Research article

Estrogen receptor-α gene haplotype is associated with primary knee osteoarthritis in Korean population

Sheng-Yu Jin^1* , Seung-Jae Hong^2* , Hyung In Yang³ , Sang-do Park³ , Myung-Chul Yoo⁴ , Hee Jae Lee¹ , Mee-Suk Hong¹ , Hae-Jeong Park¹ , Seo Hyun Yoon¹ , Bum-Shik Kim¹ , Sung-Vin Yim¹ , Hun-Kuk Park¹ and Joo-Ho Chung¹

¹  Kohwang Medical Research Institute, Department of Pharmacology, College of Medicine, Kyung Hee University, Seoul, Korea

²  Department of Internal Medicine, College of Medicine, Pochon CHA University, Sungnam, Korea

³  Division of Rheumatology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea

⁴  Department of Orthopedic Surgery, College of Medicine, Kyung Hee University, Seoul, Korea

author email corresponding author email* Contributed equally

Arthritis Res Ther 2004, 6:R415-R421doi:10.1186/ar1207

Published:	19 July 2004

Abstract

Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-α gene polymorphisms for its associations with primary knee OA, we conducted a case–control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-α gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the ER-α gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01–1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, χ² = 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that ER-α gene haplotype may be associated with primary knee OA, and genetic variations in the ER-α gene may be involved in OA.