title: Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population.
abstract: BACKGROUND
  Periodontitis is an inflammatory disease that leads to irreversible attachment loss, bone destruction and eventually tooth loss. Tumor necrosis factor (TNF), a pluripotent proinflammatory cytokine that is able to induce tissue destruction and bone resorption, has been implicated in the pathogenesis of periodontal disease.
  
  
  METHODS
  In this study, we investigated an association between chronic periodontitis and two previously described bi-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'promoter region of the TNF-alpha gene and an NcoI restriction fragment length polymorphism (RFLP) in the first intron (position +252A/G) of the lymphotoxin alpha (LT-alpha) gene. Genomic DNA was obtained from 132 patients with chronic periodontitis together with 114 age- and gender-matched unrelated control subjects.
  
  
  RESULTS
  The TNF-alpha (-308G/A) polymorphism itself showed no association with chronic periodontitis, whereas the frequency distribution of the LT-alpha (+252A/G) genotypes showed statistically significant differences between patients and the reference group. The proportion of individuals carrying the LT-alpha 1/1 genotype was significantly lower in the group of patients with chronic periodontitis (0.8%) than in the control group (8.8%) (P < 0.0094, Pcorr < 0.05). However, the significant differences in the frequencies of the combined genotypes (TNF-alpha and LT-alpha) between the control and the patient groups were found using a simulation by applying the Monte-Carlo method (P < 0.01).
  
  
  CONCLUSIONS
  Our data suggest that combined genotypes composed of the TNF-alpha and LT-alpha gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT-alpha gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population.
authors.affiliation: Department of Pathological Physiology, Clinic of Stomatology, Medical Faculty and Centre for Mathematical Modelling, Masaryk University Brno, Czech Republic.
authors.forename: Antonin
authors.initials: A
authors.lastname: Fassmann
authors.forename: Lydie Izakovicova
authors.initials: LI
authors.lastname: Holla
authors.forename: Dana
authors.initials: D
authors.lastname: Buckova
authors.forename: Anna
authors.initials: A
authors.lastname: Vasku
authors.forename: Vladimir
authors.initials: V
authors.lastname: Znojil
authors.forename: Jiri
authors.initials: J
authors.lastname: Vanek
mesh_terms: D000225:Adenine; D000328:Adult; D016022:Case-Control Studies; D002908:Chronic Disease; D018153:Czech Republic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006147:Guanine; D006801:Humans; D007438:Introns / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D010518:Periodontitis / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D000225:Adenine