Mutational analysis of cytoplasmic domain of integrin subunit alpha-1 and its association with periapical wound healing after surgical endodontic treatment

Background Numerous studies reported that the healing after surgical endodontic retreatment is influenced by multiple factors which include the genetic profile of the patient, epigenetics, and immune responses. The genes which are primarily responsible for the healing potential in different individuals are those which are involved in the regulation of the cytoskeleton and cellular adhesion which subsequently affects bone deposition and healing. Integrins are cell-surface molecules, possess a key role in the cytoskeleton and cellular adhesion. Integrin Subunit Alpha 1 (ITGA1) is one among the integrin family and helps in regulating the Epidermal Growth Factor receptor (EGFR) pathway, consequently affects proliferation and healing. The objectives of the study were to identify mutations in the cytoplasmic domain of Integrin Subunit Alpha 1 (ITGA1), to assess the expression of activated EGFR, EGFRPhospho and TC-PTP in the periapical wound and to correlate these mutations and expression patterns with periapical wound healing. Methods and findings Thirty-seven patients between ages 18-60 years reported chronic apical periodontitis of single-rooted anterior teeth with periapical radiolucency, equal or greater than 4 mm or periapical lesion in an open apex of single-rooted teeth due to trauma were included in the study from 01st June 2018 till 31st October 2019. Patients with persistent radiolucency after primary root canal treatment and endodontic retreatment were kept on follow-up for 3-4 months surgical endodontic treatment was performed in cases with persistent periapical lesions of 4mm or more in diameter. Periapical lesion sample was collected and used for (1) histo-pathological analysis after Hematoxylin & Eosin staining, (2) total DNA extraction for ITGA1 cytoplasmic domain mutational analysis and immunohistochemistry for EGFR and TCPTP. A positive correlation was observed between the expression levels of EGFRPhospho and the healing of periapical lesions. Moreover, a negative weak correlation was observed between the expression levels of EGFR and TCPTP and the healing of periapical lesions. Out of nine sequences of cytoplasmic domain of ITGA1 which were analyzed, none of them was detected with SNP. Conclusion Higher expression levels of EGFRPhospho and lower expression levels of EGFR and TCPTP were associated with patients with good healing potential in periapical area. However, immunohistochemistry scores were statistically insignificant to draw any conclusion.