Association of COMT and MAO-B gene polymorphic variants with sensitivity to dopaminergic therapy in patients with Parkinson’s disease

Introduction. Levodopa and other dopaminergic agents remain the cornerstone of pharmacotherapy for Parkinson’s disease (PD). Two enzymes play key roles in dopamine metabolism: catechol-O-methyltransferase and monoamine oxidase type B, encoded by the COMT and MAO-B genes respectively. This study aimed at analyzing potential association between dopaminergic therapy response and carrier status of COMT (rs4680) and MAO-B (rs1799836) polymorphisms in patients with PD. Materials and methods. The study included 96 PD patients at stages 2–3 on the modified Hoehn and Yahr scale. Most patients (n=64; 66.7%) received levodopa/carbidopa, with 40.6% on combined dopaminergic therapy. All patients underwent assessment of dopaminergic therapy effictiveness using the difference in motor deficit (calculated from part III of the Unified Parkinson’s Disease Rating Scale) between the worst and best states (%). COMT and MAO-B polymorhisms were detected by real-time polymerase chain reaction. Results. Allelic analysis demonstrated that carriers of the COMT gene rs4680 G allele responded better to dopaminergic therapy than A allele carriers (p = 0.038) (43.78 ± 18.15% vs 38.53 ± 16.58%; p = 0.038). Among men, we found no significant differences in therapy sensitivity related to MAO-B (rs1799836) variants, while female CC genotype carriers demonstrated better treatment response than TC heterozygotes (35.45 ± 17.78% vs 55.16 ± 11.22%; p=0.019). Conclusion. Our data suggest that in patients with PD, not only drug-induced dyskinesias and motor fluctuations, but also overall sensitivity to dopaminergic therapy may be associated with specific COMT and MAO-B polymorphisms.