Method: 1,600 radiographs obtained through the University of Pittsburgh Dental Registry and DNA Repository were screened for subjects with deep carious lesions in dentin with or without periapical lesions (3mm or bigger). DNA samples of 268 patients were sorted into two groups: 158 cases with deep carious lesions but no periapical lesions (controls) and 110 cases with periapical lesions and deep carious lesions (cases). SNPs in IRE-1 and its downstream target XBP-1 were selected for genotyping. Genotypes were generated by endpoint analysis in a real-time PCR machine and cases and controls were compared. Data were analyzed using PLINK.
Result: For IRE-1 SNPs rs196929 and rs186950, P-values of 0.05 and 0.03 were obtained, indicating frequency differences between cases and controls. Moreover, genotypic association tests indicated association between XBP-1 SNPs rs2239815 and rs2097461 with periapical lesions (P = 0.05). XBP-1 SNP rs2239815 also demonstrated statistically significant association with IRE-1 SNP variant rs116550100 (P = 0.04). The XBP-1 SNP rs2097461 was also linked to IRE-1 variant rs11655010 (P = 0.009). Haplotype analysis also showed possible bi-allelic expression: IRE-1 SNP rs16947425 did not show statistically significant association by itself but was associated when analyzed with IRE-1 SNP rs11655020 (P = 0.01).
Conclusion: Our data support the role of IRE-1 and XBP-1 in periapical lesion formation.