RELATION OF ALLELES OF THE COLLAGEN TYPE I-ALPHA-1 GENE TO BONE-DENSITY AND THE RISK OF OSTEOPOROTIC FRACTURES IN POSTMENOPAUSAL WOMEN

Background Osteoporosis is a common disorder with a strong genetic com ponent. One way in which the genetic component could be expressed is t hrough polymorphism of COLIA1, the gene for collagen type l alpha 1, a bone-matrix protein, Methods We determined the COLIA1 genotypes SS, S s,and ss in a population-based sample of 1778 postmenopausal women usi ng a polymerase-chain-reaction-based assay. We then related the genoty pes to bone mineral density and the occurrence of osteoporotic fractur es in these women. Results As compared with the 1194 women with the SS genotype, the 526 women with the Ss genotype had 2 percent lower bone mineral density at the femoral neck (P = 0.003) and the lumbar spine (P = 0.02); the 58 women with the ss genotype had reductions of 4 perc ent at the femoral neck (P = 0.05) and 6 percent at the lumbar spine ( P = 0.005). These differences increased with age (P = 0.01 for modific ation by age of the effect of COLIA1 on femoral-neck bone density, and P = 0.004 for modification of the effect on lumbar-spine bone density ). Women with the Ss and ss genotypes were overrepresented among the 1 11 women who had incident nonvertebral fractures (relative risk per co py of the s allele, 1.5; 95 percent confidence interval, 1.1 to 2.1). Conclusions The COLIA1 polymorphism is associated with reduced bone de nsity and predisposes women to osteoporotic fractures. (C) 1998, Massa chusetts Medical Society.