title: New approach to analyze genetic and clinical data in bisphosphonate-induced osteonecrosis of the jaw.
abstract: OBJECTIVE
  Osteonecrosis of the jaw (ONJ) is a major complication associated with long-term use of bisphosphonates (BP). We aimed to investigate the effect of CYP2C8 rs1934951 SNP and its relationship to a number of clinical and biochemical factors in 46 Hungarian subjects with bisphosphonate-induced ONJ.
  
  
  METHODS
  Blood samples were collected from each subject and genomic DNA was extracted. SNP analysis of CYP2C8 gene was carried out by predesigned TaqMan primer/probe sets. The genetic data together with clinical and biochemical variables were evaluated by chi-square test, logistic regression, and principal component analysis (PCA).
  
  
  RESULTS
  The risk of mandibular localization of ONJ was 19.2-fold higher in subjects with AG genotype than in normal GG genotype. PCA revealed strong positive correlations between maxillar localization of ONJ and a group of variables including intravenous BP application and serum lipid markers. Mandibular localization of ONJ was correlated positively with serum calcium, 25-hydroxy-vitamin D and PTH levels, oral BP application, and the length of BP therapy. The degree of the disease and the number of recurrences were correlated with the application of hormone-deprivation therapy for breast cancer patients.
  
  
  CONCLUSIONS
  The statistical approach applying PCA to our data may contribute to the better understanding of factors playing role in the development of bisphosphonate-induced ONJ.
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary. betti@bel1.sote.hu
authors.forename: B
authors.initials: B
authors.lastname: Balla
authors.forename: M
authors.initials: M
authors.lastname: Vaszilko
authors.forename: J P
authors.initials: JP
authors.lastname: Kósa
authors.forename: J
authors.initials: J
authors.lastname: Podani
authors.forename: I
authors.initials: I
authors.lastname: Takács
authors.forename: B
authors.initials: B
authors.lastname: Tóbiás
authors.forename: Z
authors.initials: Z
authors.lastname: Nagy
authors.forename: A
authors.initials: A
authors.lastname: Lazáry
authors.forename: P
authors.initials: P
authors.lastname: Lakatos
mesh_terms: D000225:Adenine; D061605:Administration, Intravenous; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000201:enzymology / Q000235:genetics*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy; D002118:Calcium / Q000097:blood; D065727:Cytochrome P-450 CYP2C8; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006147:Guanine; D006801:Humans; D006814:Hungary; D008055:Lipids / Q000097:blood; D008297:Male; D008336:Mandibular Diseases / Q000201:enzymology / Q000235:genetics; D008439:Maxillary Diseases / Q000235:genetics; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D012008:Recurrence; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D018931:Antineoplastic Agents, Hormonal; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D020847:Estrogen Receptor Modulators; D008055:Lipids; D010281:Parathyroid Hormone; D014807:Vitamin D; D006147:Guanine; C104450:25-hydroxyvitamin D; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D000225:Adenine; D002118:Calcium