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 stud y. 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, a nd fractures were determined radiographically. The COL1A1 genotype was asse ssed 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 o f at least one copy of the "s" allele was associated with a significant red uction in lumbar spine BMD (P = 0.02) and;an increased risk of total fractu re (P = 0.04). Urinary pyridinoline levels were significantly elevated in t hose with the risk allele (P < 0.05). Conclusion. These data support the findings that the COL1A1 gene polymorphi sm is associated with low BMD and fracture risk, and suggest a possible phy siologic effect on total body turnover of type I collagen.