Twin and family studies had shown that genetic factors are important determinants of bone mass. Multiple genes might be involved. One candidate gene, the reversion-induced LIM gene ( RIL), is a PDZ and LIM-domain-containing protein and has been localized within the cytokine cluster of chromosome 5 (5q31.1). In a genetic study of 370 adult Japanese women, we investigated the correlation between radial bone mineral density (BMD) and a genetic variation (-3333T-->C) of the 5'-flanking region of RIL gene. A significant association was identified between the RIL variation -3333T-->C and radial BMD ( r=0.15, P=0.003). The variation of the RIL locus may be an important determinant of osteoporosis.