BACKGROUND: Osteoporosis is a common disorder with a strong genetic component. One way in which the genetic component could be expressed is through polymorphism of COLIA1, the gene for collagen type Ialpha1, a bone-matrix protein. METHODS: We determined the COLIA1 genotypes SS, Ss, and ss in a population-based sample of 1778 postmenopausal women using a polymerase-chain-reaction-based assay. We then related the genotypes to bone mineral density and the occurrence of osteoporotic fractures 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 percent 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 modification 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 111 women who had incident nonvertebral fractures (relative risk per copy of the s allele, 1.5; 95 percent confidence interval, 1.1 to 2.1). CONCLUSIONS: The COLIA1 polymorphism is associated with reduced bone density and predisposes women to osteoporotic fractures.

Age Factors, Aged, Aged, 80 and over, Alleles, Bone Density/*genetics, Collagen/*genetics, Female, Fractures, Bone/etiology/*genetics, Genotype, Humans, Middle Aged, Osteoporosis, Postmenopausal/complications/*genetics, Polymorphism, Genetic, Postmenopause, Regression Analysis, Risk Factors
New England Journal of Medicine
Erasmus MC: University Medical Center Rotterdam

Uitterlinden, A.G, Burger, H, Huang, Q, Yue, F, McGuigan, F.E, Grant, S.F.A, … Hofman, A. (1998). Relation of alleles of the collagen type Ialpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women. New England Journal of Medicine. Retrieved from