Association of polymorphism at the type I collagen (COL1A1) locus with reduced bone mineral density, increased fracture risk, and increased collagen turnover.

OBJECTIVE: To examine the relationship between a common polymorphism within intron 1 of the COL1A1 gene and osteoporosis in a nested case-control study. METHODS: We studied 185 healthy women (mean +/- SD age 54.3+/-4.6 years). Bone mineral density (BMD) was measured using dual x-ray absorptiometry, and fractures were determined radiographically. The COL1A1 genotype was assessed using the polymerase chain reaction and Bal I endonuclease digestion. RESULTS: Genotype frequencies were similar to those previously observed and in Hardy-Weinberg equilibrium: SS 61.1%, Ss 36.2%, and ss 2.7%. Carriage of at least one copy of the "s" allele was associated with a significant reduction in lumbar spine BMD (P = 0.02) and an increased risk of total fracture (P = 0.04). Urinary pyridinoline levels were significantly elevated in those with the risk allele (P < 0.05). CONCLUSION: These data support the findings that the COL1A1 gene polymorphism is associated with low BMD and fracture risk, and suggest a possible physiologic effect on total body turnover of type I collagen.