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External apical root resorption (EARR) is a frequent iatrogenic effect of orthodontic treatment. The way root-filled teeth respond to orthodontic forces with respect to EARR has been reported as varying widely between individuals. Genetic variants in the interleukin-1 gene have been associated with an increased risk of experiencing postorthodontic EARR on vital teeth. The objective of this study is to determine whether variants in the interleukin-1 gene have a positive or negative influence on EARR on teeth that have been endodontically treated.Ninety-three orthodontic patients underwent genetic screening for 2 single nucleotide polymorphisms (rs1800587, rs1143634) in the IL1 gene cluster. Subjects were divided into 2 groups depending on the presence (affected group) or absence (control group) of more than 2 mm of EARR on root-filled teeth after orthodontic treatment as shown by radiography. Logistic regression analysis was used to obtain adjusted estimates of EARR and IL1 polymorphisms. Allele frequencies, genotype distributions, and adjusted odds ratios were also calculated (95% confidence interval).No positive or negative statistical association was found between postorthodontic treatment EARR in root-filled teeth and genetic variations in IL1A (P > .05). A direct relationship was found for the IL1B gene in the comparative analysis of homozygous subjects (2/2[TT]) and (1/1[CC]), which led to an increased risk of experiencing postorthodontic treatment EARR in root-filled teeth (odds ratio = 11.59; P = .006; confidence interval, 95%) and (odds ratio = 2.54; P = .035; confidence interval, 95%), respectively.The development of EARR in subjects with root-filled teeth who undergo orthodontic treatment might be attributable to genetic variations in the interleukin-1β gene (rs1143634).