No association between selected candidate gene polymorphisms and severe chronic periodontitis.
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 >or=35 years of age with eight or more teeth having >or=5 mm of proximal clinical attachment loss. Controls (N=82) were >or=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 beta-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.
Wohlfahrt
Johan C
JC
Department of Preventive Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
Wu
Tianxia
T
Hodges
James S
JS
Hinrichs
James E
JE
Michalowicz
Bryan S
BS
D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002908:Chronic Disease; D053222:Fas Ligand Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D053495:Osteopontin; D053244:Osteoprotegerin; D010518:Periodontitis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019713:Receptors, CCR5 / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000235:genetics; D023083:beta-Defensins / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C406407:DEFB1 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006023:Glycoproteins; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D019713:Receptors, CCR5; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506030:TNFRSF11B protein, human; D048069:Tumor Necrosis Factors; D023083:beta-Defensins; D053495:Osteopontin; D018799:Intercellular Adhesion Molecule-1