|Budget Amount *help
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
There are significant sex differences regarding the prevalence and clinical manifestations of osteoarthritis (OA) and rheumatoid arthritis (RA). OA and RA are more likely to occur in women, suggesting the role of sex hormones in the pathogenesis of diseases. In addition, both diseases have genetic components. From these findings, we investigated the association of polymorphisms of sex hormone-related genes with OA and RA patients.
Some variant of estrogen receptor gene is a genetic marker for generalized OA which is one of subtypes of OA (Ushiyama et al. J Rheumatol, 1998). On the other hand, there was no significant association between the vitamin D receptor gene variants and OA of the hand, hip, knee, or polyarticular involvement (Huang et al. Rheumatology 1999).
In patients with RA, some variants of the estrogen receptor gene are related to the onset of female RA in certain age periods, suggesting the role of the interaction between the estrogen receptor gene and serum levels of estrogen at the onset of the disease (Ushiyama et al. Ann Rheum Dis 1999). In contrast, shorter CAG repeats of the androgen receptor gene, presenting high levels of transactivation activity, is related to the onset of male RA during younger ages (Kawasaki et al. Ann Rheum Dis 1999). Shorter CAG repeats were also associated with male patients with ankylosing spondylitis (Mori K et al. Rhematology 2000). Furthermore, CYP17 gene polymorphisms, which are related to serum sex hormone production, are related to onset of RA (Huang et al. Clin Exp Rheumatol 1999).
We demonstrate the gene expression of both estrogen receptor α and β in human articular chondrocytes and the expression levels of both genes were significantly higher in men than in women. These results suggests that estrogen affects cartilage metabolism directly via receptors (Ushiyama et al. Osteoarthritis Cart, 1999).