**10. Estrogen receptor alpha (***ESR- α***) gene**

The estrogen receptor (*ESR-α*) is a ligand-activated transcription factor composed of several domains essential for hormone binding, DNA binding, and activation of transcription. Alternative splicing results in several *ESR-α* mRNA transcripts, which differ primarily in their 5′ untranslated regions. The translated receptors show less variability [4, 119]. Ponglikitmongkol *et al*. [120, 121] showed that the human *ESR-α* gene is more than 140 kb long. It contains eight exons, and the position of its introns has been highly conserved, being, for example, remarkably similar to those of one of the chicken thyroid hormone receptor genes. Sputnik *et al*. [122] reported that *ESRα* isoform is a ligand-activated transcription factor composed of several essential domains for hormone binding and activation of transcription. *ESRα* is an essential mediator in the signal transduction pathway. Jin *et al.* [123] reported that Estrogen receptors (*ESR-α*) are known to play an essential role in the pathophysiology of Osteoarthritis. To investigate *ESRα* gene polymorphisms for its association with primary knee osteoarthritis, they conducted a casecontrol association study in patients with primary knee osteoarthritis and healthy individual in the Korean population. Jin *et al.* (2004) investigated the association between haplotypes of three polymorphism in *PVU II* in intron 1(IVS1-397 T/C), Xba I in intron 1(IVS1-351A/G) and Big I in exon 8 (exon8 229G/A) of *ESR-α* gene and primary knee OA in the Korean population, first two SNP in intron one also investigated by Bergink et al. [124] in Rotterdam population. Ushiyama *et al*. [125] found on *ESR-α* gene association between a genotype of *PVU II* and Xba I polymorphisms in Intron 1 and generalized Osteoarthritis with a severe radiographic change in the Japanese population.
