Type I collagen alpha1 Sp1 transcription factor binding site polymorphism is associated with reduced risk of hip osteoarthritis defined by severe joint space narrowing in elderly women

Arthritis Rheum. 2005 May;52(5):1431-6. doi: 10.1002/art.21011.

Abstract

Objective: A common G/T substitution at an Sp1 binding site in intron 1 of the COL1A1 gene has been reported to be associated with reduced bone mineral density and increased risk of osteoporotic fracture. The purpose of this study was to examine whether there is an association between COL1A1 Sp1 polymorphism and radiographic osteoarthritis (OA) of the hip in elderly women in the Study of Osteoporotic Fractures.

Methods: Radiographic hip OA status of subjects was defined by the presence of 1 of the following criteria in either hip: a joint space narrowing (JSN) score of >/=3, a Croft summary grade of >/=3, or both definite (score >/=2) osteophytes and JSN in the same hip. Cases of radiographic OA of the hip were further subdivided into those with JSN score >/=3 and those with a femoral osteophyte score >/=2 and JSN score </=2. The COL1A1 Sp1 polymorphism was genotyped using allele-specific kinetic polymerase chain reaction in 4,746 women. Multivariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results: Radiographic OA of the hip was present in 571 women (12%). Of these patients, 325 (57%) had severe JSN (score >/=3), and 131 (23%) had moderate or moderate-to-severe femoral osteophytosis (score >/=2). There was no association of the T/T genotype with either radiographic hip OA or radiographic hip OA characterized by osteophytosis. For radiographic OA of the hip characterized by moderate-to-severe JSN, the odds of disease were significantly reduced among subjects with the T/T compared with the G/G genotype (OR 0.30, 95% CI 0.11-0.81, P = 0.02) and did not change after adjustment for potential confounders (OR 0.36, 95% CI 0.13-0.99, P = 0.048).

Conclusion: The T/T genotype of the COL1A1 Sp1 polymorphism was associated with a reduced risk of radiographic OA of the hip characterized by JSN. This association should be confirmed in other populations to determine if mechanistic studies are warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Aged
  • Collagen Type I / genetics*
  • Female
  • Humans
  • Osteoarthritis, Hip / diagnostic imaging
  • Osteoarthritis, Hip / genetics*
  • Osteoarthritis, Hip / pathology*
  • Polymorphism, Genetic*
  • Radiography
  • Risk Factors
  • Severity of Illness Index
  • Sp1 Transcription Factor / genetics*

Substances

  • Collagen Type I
  • Sp1 Transcription Factor