POLYMORPHISMS OF THE INTERLEUKIN-6 GENE ARE ASSOCIATED WITH BONE-MINERAL DENSITY

Genetic factors play an important role in determining bone mass and se veral genes probably act as regulators of this process, Interleukin-6 (IL-6) is a candidate gene for regulation of bone density, since it ha s stimulatory effects on cells of the osteoclast lineage and has been implicated in the pathogenesis of bone loss associated with estrogen d eficiency, Here we studied the relationship between bone mineral densi ty (BMD) and a polymorphic AT rich minisatelite repeat in the 3' flank of the IL-6 gene in a cohort of 200 women, Six length variants were i dentified (designated A-Fl, but four of these were rare such that the vast majority of individuals fell into one of two common genotypes: F/ F (58.5%) and C/F (27.5%), There was a significant relationship betwee n IL-6 genotype and bone mass at the lumbar spine as determined by ana lysis of variance (p = 0.04) and a similar trend for bone mass at the femoral neck (p = 0.11), When BMD values were compared in the two comm on genotypes, we found that spine BMD values were significantly higher in the C/F genotype (mean +/- SEM = 0.94 +/- 0.04 g/cm(2)) as compare d with the F/F genotype (0.81 +/- 0.02 g/cm(2); p = 0.012). A similar trend was seen for hip BMD values, but here, the difference failed to reach statistical significance (p = 0.06). Further analysis showed tha t genotype-specific effects on bone mass were observed in both premeno pausal and postmenopausal women and did not increase with age, suggges ting that the association between IL-6 polymorphisms and bone density may be mediated by an effect on peak bone mass, rather than rate of bo ne loss, We conclude that bone mass is associated with two common poly morphisms of the IL-6 gene, Although the mechanisms that underlie this association will require further research, our data suggest that poly morphic variation at the IL-6 gene locus may contribute to the genetic regulation of bone mass. (C) 1997 by Elsevier Science Inc. All rights reserved.