No association between selected candidate gene polymorphisms and severe chronic periodontitis

Johan C. Wohlfahrt, Tianxia Wu, James S. Hodges, James E. Hinrichs, Bryan S. Michalowicz

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Background: Chronic periodontitis (CP) risk is influenced by environmental and genetic factors. Using a case-control design, we tested for associations between CP and selected DNA sequence variations (single nucleotide polymorphisms [SNPs]) in or near genes coding for proteins that play a role in the pathogenesis of this disease. Methods: DNA was analyzed from 219 whites who were examined clinically. Cases (N = 137) were ≥35 years of age with eight or more teeth having ≥5 mm of proximal clinical attachment loss. Controls (N = 82) were ≥45 years of age with minimal or no proximal attachment loss or pocketing. Nine diallelic polymorphisms (gene and SNP descriptor) were studied in subjects: cytotoxic T-lymphocyte antigen-4 (CTLA-4, 49 A>G), human β-defensin-1 (DEFB1, 692 G>A), intercellular adhesion molecule-1 (ICAM-1, 1548 A>G), Fas ligand (fasL, -844 C>T), inducible costimulator (ICOS, 3990 G>T), interleukin-6 (IL-6, -174 G>C), cysteine-cysteine chemokine receptor-5 (CCR5, 59653 C>T), osteoprotegerin (OPG, 245 T>G), and osteopontin (OPN, 707 C>T). Genotypes were determined using an automated fluorogenic 5′-nuclease, polymerase chain reaction-based assay. Gender and smoking history (pack-years) were included as covariates in logistic regression analyses. Results: Heavy smoking (>10 pack-years) and male gender were significantly associated with disease (P <0.001). For all SNPs tested, the allele frequencies and distributions of genotypes did not differ between cases and controls (P>0.05). No unadjusted or adjusted odds ratios (comparing genotypes in cases versus controls) were significantly different than 1.0 (P>0.05) under any additive, dominant, or recessive inheritance model. Conclusions: None of the SNPs tested were strongly associated with generalized severe chronic periodontitis in North American whites. A potentially more fruitful approach in future studies will be to test for associations between periodontitis and haplotype blocks constructed from either multiple SNPs in candidate gene regions or from panels of markers that span the entire genome.

Original languageEnglish (US)
Pages (from-to)426-436
Number of pages11
JournalJournal of periodontology
Volume77
Issue number3
DOIs
StatePublished - Mar 2006

Keywords

  • Case-control studies
  • Cytokines
  • Genetics
  • Inflammation
  • Periodontitis
  • Polymorphism
  • Single nucleotide

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