Association of Polymorphism at the Type I Collagen (COL1A1) Locus With Reduced Bone Mineral Density, Increased Fracture Risk, and Increased Collagen Turnover

Arthritis Rheum. 1999 Feb;42(2):285-90. doi: 10.1002/1529-0131(199902)42:2<285::AID-ANR10>3.0.CO;2-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Amino Acids / urine
  • Bone Density / genetics*
  • Bone Density / physiology
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Femur Neck / diagnostic imaging
  • Femur Neck / physiology
  • Fractures, Spontaneous / genetics*
  • Fractures, Spontaneous / urine
  • Haplotypes / genetics
  • Humans
  • Introns / genetics
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / injuries
  • Lumbar Vertebrae / physiology
  • Middle Aged
  • Osteoporosis, Postmenopausal / genetics*
  • Osteoporosis, Postmenopausal / urine
  • Polymorphism, Genetic*
  • Procollagen / genetics*
  • Procollagen / metabolism
  • Spinal Fractures / genetics
  • Spinal Fractures / urine
  • Thoracic Vertebrae / diagnostic imaging
  • Thoracic Vertebrae / injuries
  • Thoracic Vertebrae / physiology

Substances

  • Amino Acids
  • Procollagen
  • pyridinoline
  • deoxypyridinoline