The use of chronic gingivitis as reference status increases the power and odds of periodontitis genetic studies: a proposal based in the exposure concept and clearer resistance and susceptibility phenotypes definition.
OBJECTIVE
Current literature on chronic periodontitis genetics encompasses numerous single nucleotide polymorphisms-focused case-control studies with inconsistent and controversial results, which typically disregards the exposure concept embraced by case-control definition. Herein, we propose a case-control design reappraisal by clear phenotype selection, where chronic gingivitis represents a genetically resistant phenotype/genotype opposing the susceptible cohort.


METHODS
The hypothesis was tested in healthy, chronic periodontitis and gingivitis groups through Real-time PCR-based allelic discrimination of classic variants IL1B-3954, IL6-174, TNFA-308, IL10-592 and TLR4-299.


RESULTS
Observed allele/genotype frequencies characterize the healthy group with an intermediate genetic profile between periodontitis and gingivitis cohorts. When comparing genotype/allele frequencies in periodontitis versus healthy and periodontitis versus gingivitis scenarios, the number of positive associations (2-4) and the degree of association (p and odds ratio values) were significantly increased by the new approach proposed (periodontitis versus gingivitis), suggesting the association of IL1B-3954, TNFA-308, IL10-592 and TLR4-299 with periodontitis risk. Power study was also significantly improved by the new study design proposed when compared to the traditional approach.


CONCLUSIONS
The data presented herein support the use of new case-control study design based on the case-control definition and clear resistance/susceptibility phenotypes selection, which can significantly impact the study power and odds of identification of genetic factors involved in PD.
Department of Biological Sciences, School of Dentistry of Bauru, São Paulo University (FOB/USP), Bauru, SP, Brazil.
Gustavo Pompermaier
GP
Garlet
Ana Paula Favaro
AP
Trombone
Renato
R
Menezes
Ariadne
A
Letra
Carlos Eduardo
CE
Repeke
Andreia Espindola
AE
Vieira
Walter
W
Martins
Lucimara Teixeira das
LT
Neves
Ana Paula
AP
Campanelli
Carlos Ferreira Dos
CF
Santos
Alexandre R
AR
Vieira
D016022:Case-Control Studies; D002908:Chronic Disease; D055113:Chronic Periodontitis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005891:Gingivitis / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012107:Research Design; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D053583:Interleukin-1beta; D015850:Interleukin-6; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10