Chronic apical periodontitis is a chronic inflammatory condition characterized by periapical tissue destruction and alveolar bone resorption as a result of the host response to pulpal infection, often presenting asymptomatically. The aim of this study is to comprehensively evaluate the relationship between genetic polymorphisms and periapical lesion healing in individuals with chronic apical periodontitis at clinical and radiological levels. Despite standardized root canal treatment protocols, variability in healing outcomes among individuals suggests a potential role of genetic factors in this process.

This prospective observational study will include patients diagnosed with chronic apical periodontitis based on clinical and radiographic findings. All participants will undergo standardized endodontic treatment. At baseline, periapical radiography and cone-beam computed tomography (CBCT) will be performed to enable three-dimensional volumetric assessment. Follow-up evaluations will be conducted at 6 months with clinical examination and periapical radiography, and at 12 months with repeat CBCT imaging to assess volumetric changes in lesion size. All radiographic procedures will be performed in accordance with the ALARA principle, using an endodontic field of view (FOV).

Prior to treatment, saliva samples will be collected for DNA isolation, and single nucleotide polymorphisms in selected cytokine gene regions will be analyzed. The primary outcome measure will be the change in periapical lesion volume over time, which will be statistically evaluated in relation to genetic profiles.

This comprehensive approach is expected to enhance the understanding of healing mechanisms in apical periodontitis, improve the predictability of treatment outcomes, and contribute to the development of personalized, risk-based treatment strategies in endodontic practice.

Inclusion Criteria:

• Patients aged between 18 and 65 years
• Devital mandibular molar teeth with asymptomatic apical periodontitis
• Teeth showing negative response to percussion and palpation tests
• Teeth with negative responses to cold test and electric pulp testing
• Teeth with a Periapical Index (PAI) score of 3 or 4
• Patients classified as ASA I
• Patients without any genetic disorders (e.g., Down syndrome, congenital insensitivity to pain, etc.)

Exclusion Criteria:

• Teeth with internal or external resorption
• Teeth with a history of trauma
• Teeth with vertical or horizontal root fractures
• Teeth with grade 3 mobility and loss of function
• Teeth that cannot be isolated with rubber dam or are not restorable
• Pregnant women or patients with suspected pregnancy
• Root canal curvature greater than 25° according to Schilder's classification
• Patients with generalized periodontitis
• Presence of periodontal pocket depth greater than 3 mm in the involved tooth
• Patients classified as ASA II or higher
• Presence of preoperative swelling, sinus tract, or pain on palpation
• Patients with bruxism
• Teeth with suspected periodontal-endodontic lesions
• Teeth with a PAI index below 2 or above 5

Patients aged between 18 and 65 years who present with non-vital teeth showing negative responses to cold testing and electric pulp testing, negative responses to percussion and palpation tests, and radiographic evidence (via intraoral periapical radiography) of apical radiolucency with a Periapical Index (PAI) score of 3 or 4 in mandibular molar teeth will be included in the study.