Host genetic and immunological factors associated with root canal treatment outcomes: a systematic review

Abstract Background Outcomes of root canal treatment, such as postoperative pain and periapical healing, differ from one patient to another. Host genetic variation and the immune response may contribute to these differences, but this evidence has yet to be brought together and critically appraised. Aim To appraise the evidence linking host genetic variation and immune status with the outcomes of root canal treatment. Methods The review followed PRISMA 2020 and was registered in PROSPERO (CRD420261288360). PubMed, Scopus, Web of Science and Google Scholar were searched up to 1 March 2026. Study selection, data extraction and Newcastle-Ottawa risk-of-bias scoring were carried out in duplicate, and the evidence was summarised narratively in three themes. Results Fourteen reports, representing seven independent study populations (62–378 participants), were included; several reports shared samples. For postoperative pain and oral health-related quality of life, variants in MTNR1A , COX-2 , NOS2 , SOCS1 and IL1RN were associated with outcomes in single populations, findings for HTR2A were inconsistent, and no associations were found for COMT , OPRM1 , IL1A or IL10 . For persistent apical periodontitis, associations were reported for IL1B , FcγRIIA , RANK , RANKL and TNF-α variants, but the IL1B association was not confirmed in a second population, and studies of other immune, bone-remodelling and hormone-related genes were negative. Nonspecific immune status predicted periapical healing in one cohort. All reports were rated at low risk of bias, but no association was replicated for the same outcome in an independent population. Conclusion Evidence from a small number of observational studies, several drawn from overlapping samples, suggests that genetic variants in pain-modulating, immune-regulatory and bone-remodelling pathways, and host immune status, may be associated with postoperative pain, oral health-related quality of life and periapical healing after root canal treatment. These associations have been inconsistent, have not been replicated in independent populations, and do not currently support genetic or immunological testing in routine endodontic practice.