title: Association between osteoprotegerin G1181C and T245G polymorphisms and diabetic charcot neuroarthropathy: a case-control study.
abstract: OBJECTIVE
  Charcot neuroarthropathy is a disabling complication of diabetes. Although its pathogenesis remains unknown, we suppose that genetics may play a relevant role.
  
  
  METHODS
  We performed a case-control study with 59 subjects with diabetic Charcot neuroarthropathy (Ch group), 41 with diabetic neuropathy without Charcot neuroarthropathy (ND group), and 103 healthy control subjects (H group) to evaluate the impact of two single nucleotide polymorphisms (SNPs) of the osteoprotegerin gene (G1181C and T245G) on the risk of Charcot neuroarthropathy.
  
  
  RESULTS
  Regarding the SNPs of G1181C, we found a significant linkage between the G allele and Charcot neuroarthropathy (Ch vs. ND, odds ratio [OR] 2.32 [95% CI 1.3-4.1], P = 0.006; Ch vs. H, 2.10 [1.3-3.3], P = 0.002; and ND vs. H, 0.90 [0.7-1.9], P = 0.452); similarly, we found a linkage with the G allele of T245G (Ch vs. ND, 6.25 [2.2-19.7], P < 0.001; Ch vs. H, 3.56 [1.9-6.7], P = 0.001; and ND vs. H, 0.54 [0.6-5.7], P = 0.304), supporting a protective role for the allele C and T, respectively. For this reason we investigated the frequency of the protective double homozygosis CC + TT (7% in Ch) that was significantly lower in Ch compared with H (0.18 [0.06-0.5], P = 0.002) and with ND (0.17 [0.05-0.58], P = 0.006), whereas there was no difference between H and ND (1.05 [0.43-2.0], P = 0.468). In a multivariate logistic backward regression model, only weight and the lack of CC and TT genotypes were independently associated with the presence of Charcot neuroarthropathy.
  
  
  CONCLUSIONS
  This is the first study that shows an association between genetic regulation of bone remodeling and Charcot neuroarthropathy.
authors.affiliation: Institute of Internal Medicine, Policlinico A. Gemelli, Rome, Italy. dario.pitocco@rm.unicatt.it
authors.forename: Dario
authors.initials: D
authors.lastname: Pitocco
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zelano
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Gioffrè
authors.forename: Enrico
authors.initials: E
authors.lastname: Di Stasio
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaccardi
authors.forename: Francesca
authors.initials: F
authors.lastname: Martini
authors.forename: Tittania
authors.initials: T
authors.lastname: Musella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scavone
authors.forename: Marco
authors.initials: M
authors.lastname: Galli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Caputo
authors.forename: Lorena
authors.initials: L
authors.lastname: Mancini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ghirlanda
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003929:Diabetic Neuropathies / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D053244:Osteoprotegerin