title: A genetic association study of single nucleotide polymorphisms in FGFR1OP2/wit3.0 and long-term atrophy of edentulous mandible.
abstract: BACKGROUND
  After dental extraction, the external surface of alveolar bone undergoes resorption at various rates, and a group of patients develop excessive jawbone atrophy. Oral mucosa overlying the atrophied jawbone is unusually thin; therefore, we have hypothesized that excessive jawbone atrophy may be associated with abnormal oral mucosa contraction. FGFR1OP2/wit3.0, a cytoskeleton molecule initially identified in oral wound fibroblasts, has been shown to induce oral mucosa contraction after dental extraction. This study examined the genetic association between single nucleotide polymorphisms (SNPs) of FGFR1OP2/wit3.0 and excessive atrophy of edentulous mandible.
  
  
  RESULTS
  First, the expression of FGFR1OP2/wit3.0 was determined in gingival tissues of 8 subjects before and after dental extraction. In situ hybridization revealed that all subject increased FGFR1OP2/wit3.0 expression in the post-operative oral mucosa tissues; however, significantly high levels of FGFR1OP2/wit3.0 were observed in 3 out of 8 subjects. In a separate study, 20 long-term edentulous subjects (66.4 ± 9.4 years) were recruited. Tag-SNPs in the FGFR1OP2/wit3.0 allele were determined by Taqman-based polymerase chain reaction. The mandibular bone height was determined following the American College of Prosthodontists (ACP) protocol. Subjects with minor allele of rs840869 or rs859024 were found in the highly atrophied group by the ACP classification (Chi square test, p = 0.0384 and p = 0.0565, respectively; Fisher's Exact, p= 0.0515 and p = 0.2604, respectively). The linear regression analysis indicated a suggestive association between rs859024 and the decreased bone heights (Mann-Whitney, p = 0.06). The average bone height of the subjects with rs840869 or rs859024 minor alleles (10.6 ± 3.2 mm and 9.6 ± 3.2 mm, respectively) was significantly smaller than that of those subjects with the major alleles (14.2 ± 4.5 mm, p<0.05).
  
  
  CONCLUSIONS
  The patients with the minor allele of rs840869 or rs859024 were associated with excessive atrophy of edentulous mandible. This study may provide the basis for a genetic marker identifying susceptible individuals to develop jawbone atrophy after dental extraction.
authors.affiliation: The Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, University of California Los Angeles School of Dentistry, Los Angeles, California, United States of America.
authors.forename: Jaijam
authors.initials: J
authors.lastname: Suwanwela
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Lee
authors.forename: Audrey
authors.initials: A
authors.lastname: Lin
authors.forename: T Cemal
authors.initials: TC
authors.lastname: Ucer
authors.forename: Hugh
authors.initials: H
authors.lastname: Devlin
authors.forename: Janet
authors.initials: J
authors.lastname: Sinsheimer
authors.forename: Neal R
authors.initials: NR
authors.lastname: Garrett
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D000483:Alleles; D001284:Atrophy / Q000235:genetics; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D007568:Jaw / Q000473:pathology*; D007575:Jaw, Edentulous / Q000235:genetics*; D008334:Mandible; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: C117597:CEP43 protein, human; D005819:Genetic Markers; D011518:Proto-Oncogene Proteins