A large Icelandic family with early osteoarthritis of the hip associated with a susceptibility locus on chromosome 16p

Arthritis Rheum. 2001 Nov;44(11):2548-55. doi: 10.1002/1529-0131(200111)44:11<2548::aid-art435>3.0.co;2-s.


Objective: To describe a large kinship with inherited hip osteoarthritis (OA) and its associated susceptibility locus.

Methods: Four generations of a kinship with familial hip OA were identified and characterized by family history and by clinical, radiographic, and histopathologic examination. In the genome-wide search for a susceptibility locus, OA cases were defined as those who had undergone total hip replacement associated with a clinical and radiographic diagnosis of hip OA. A genome-wide scan was performed using a framework set of microsatellite markers with an average spacing of 10 cM.

Results: The hip OA of this family was indistinguishable from that of idiopathic, nonfamilial hip OA. There was no apparent evidence of spondyloepiphyseal dysplasia or other dysplasias usually associated with mutations in collagen genes. The genome-wide scan revealed a locus on chromosome 16p between 28 cM and 47 cM from the telomere, and this locus met the criteria for suggestive linkage (multipoint allele-sharing logarithm of odds [LOD] score 2.58, P = 1.6 x 10(-4)). Two additional regions with LOD scores of >1.5 were obtained.

Conclusion: We have identified and described the largest kinship with familial hip OA reported to date. Evidence for linkage in this family suggests that a gene for susceptibility to hip OA exists on chromosome 16p. This represents an independent identification of a susceptibility locus previously reported for hip OA in this geographic region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Arthroplasty, Replacement, Hip
  • Chromosomes, Human, Pair 16*
  • Female
  • Femur Head / diagnostic imaging
  • Femur Head / pathology
  • Genetic Predisposition to Disease*
  • Humans
  • Iceland
  • Lod Score
  • Male
  • Middle Aged
  • Osteoarthritis, Hip / diagnostic imaging
  • Osteoarthritis, Hip / genetics*
  • Osteoarthritis, Hip / physiopathology
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteoarthritis, Knee / genetics
  • Pedigree
  • Phenotype
  • Radiography