The SDHD H102R Variant is a Genetic Risk Factor for Head and Neck Paraganglioma in the Russian Population

Introduction: Head and neck paraganglioma (HNPGL) is an extremely rare tumor with a strong genetic predisposition. Approximately 40% of HNPGLs are associated with mutations in the SDHx genes, which can harbor pathogenic genetic alterations specific to certain populations. In our previous research, we identified a frequent genetic variant—NM_003002: c.305A>G, p.H102R (chr11:111959726, rs104894302)—in the SDHD gene among Russian patients diagnosed with HNPGL. The present study analyzed expanded case and control cohorts to accurately estimate the association between this variant and the risk of developing the disease. Methods: The study comprised two expanded cohorts: 187 patients with HNPGL and 1,055 healthy individuals of Russian descent. Genetic testing for the SDHD H102R variant was performed using targeted sequencing on an Illumina platform. Results: The SDHD H102R variant was detected in 7.5% of the overall patient cohort and in 19% of all SDHx-mutated cases. Furthermore, the variant was present in one-third of all SDHD mutation carriers. In the control cohort, the frequency of the SDHD H102R variant was 0.6%. The adjusted odds ratio, accounting for sex and age covariates, was 8.7 (95% CI: 2.3–32.6, p = 0.001). Conclusion: This case-control study demonstrates a strong association between the SDHD H102R variant and the risk of developing HNPGL in the Russian population.