Evaluation of histamine 1 receptor polymorphisms in patients with subjective tinnitus and their effects on treatment response efficacy

This study aimed to investigate the effects of Histamine 1 (H1) receptor polymorphisms on tinnitus and the response to betahistine treatment, using the Tinnitus Handicap Inventory (THI) and Tinnitus Loudness Matching tests. A total of 75 patients with subjective tinnitus (42 females, 33 males), aged 18-65 years, who presented to the Otolaryngology Outpatient Clinic of Tokat Gaziosmanpaşa University Faculty of Medicine and met the inclusion criteria were enrolled. Age-matched individuals without tinnitus were included as a control group. Ethical approval was obtained from the Ethics Committee for Non-Interventional Scientific Research of Tokat Gaziosmanpaşa University. At baseline, audiometric evaluations were performed, tinnitus frequency and loudness were recorded, and the THI was administered. All patients received betahistine treatment and were re-evaluated after three months. A reduction of ≥7 points in THI or ≥15 dB in loudness matching was considered a significant treatment response. Genotyping of the 1068-A/G (rs2067468) and Leu449Ser (rs2067470) polymorphisms in the H1 receptor gene was performed using PCR-RFLP analysis of venous blood samples. There was no significant difference in genotype or allele distribution of the 1068-A/G and Leu449Ser polymorphisms between the tinnitus and control groups (p=0.448 and p=0.511, respectively). However, for the 1068-A/G polymorphism, a significant difference in loudness matching was found between treatment responders and non-responders (p=0.014). In addition, none of the five patients carrying the G allele benefited from betahistine treatment. No significant association was observed between genotype and treatment response based on THI scores (p=1.000). In conclusion, based on the fact that there were no patients with the G allele in the group that benefited from treatment, we concluded that the presence of the G allele in the H1 receptor gene negatively affects the response to betahistine treatment. However, we believe that this issue should be supported by more comprehensive and advanced studies. Keywords: Tinnitus, H1 receptor gene, 1068-A/G polymorphism, Leu449Ser polymorphism, betahistine Suppoerted by: TOGÜ-BAP 2024/91