Genetic Association Study of CASP1 and EARR During Orthodontia

Objective: Genetic variation in the IL-1ß gene is associated with increased external-apical-root-resorption (EARR) in orthodontic patients. Caspase 1 (interleukin converting enzyme) is an upstream catalyst for the activation of IL-1ß in both monocytic and osteoclastic cells. This study investigates the potential association of two single nucleotide polymorphisms (SNPs) in CASP1, rs530537 and rs580253, with EARR of the maxillary-incisors in orthodontic patients. The null-hypothesis states that variation in CASP1 is not associated with EARR. The alternative-hypothesis states that variation in CASP1 is associated with EARR.

Method: DNA was isolated from the buccal swabs of 159 Caucasian orthodontic patients (22-affected, 143-control) with informed consent. Taqman®-based genotyping was utilized for the allelic discrimination of rs530537 and rs580253 on the Roche LightCycler480. Pre/post-treatment radiographs were analyzed qualitatively by three investigators for EARR of the maxillary-incisors. Subjects were considered to be “affected” when at least two-of-three investigators agreed that EARR was present on at least one of the subject's maxillary-incisors. Chi-square analyses were used to assess Hardy-Weinberg equilibrium in the unaffected, and the association of rs530537 and rs580253 CASP1 genotypes with EARR in the affected and unaffected groups, with significance at (p<0.05). All samples were genotyped for rs530537, a subset of 74 were genotyped for rs580253.

Result: All rs530537 and rs580253 genotypes of the unaffected were in Hardy-Weinberg equilibrium. Chi-square analysis yielded p=0.89 and p=0.14 respectively for rs530537 and rs580253.

Conclusion: While the null-hypothesis could not be rejected for rs530537, rs580253 and EARR, the data are suggestive that analysis of additional subjects could reveal a small effect of the rs580253 CASP1, which is a functional polymorphism, on EARR. If demonstrated, this would indicate that CASP1 (or a locus in linkage disequilibrium with it) plays a role in EARR during orthodontic treatment. Additional subjects are being analyzed along with analysis of rs580253 CASP1 genotypes.