Objective: To investigate the association of the most common functional catechol-O-methyltransferase (COMT) gene haplotypes with risk to develop of Parkinson’s disease (PD) and the association of COMT haplotypes with clinical symptoms and pharmacotherapy in PD patients.

Background: The single nucleotide polymorphisms (SNPs) in COMT gene may be associated with the risk of PD, and may also determine individual variations in clinical features, especially the therapeutic response to levodopa. However, the role of the combined functional COMT genotypes in People’s Republic of China has not been examined.

Methods: We adopted 143 idiopathic PD patients and 157 age-and sex-matched healthy individuals in this study. Each participant was genotyped for five SNPs in the COMT gene (formed by SNPs): rs6269 A > G; rs4633 C > T; rs6267 G > T; rs4818 C > G; and rs4680 A > G. Meanwhile, we compared the association between the studied gene polymorphisms and the basic clinical features of PD patients.

Results: The frequency of the COMT haplotypes didn’t differ significantly between PD patients and controls. While the rs6269 (GG) genotype (P=0.09), minor G allele of rs6269 (P=0.09), minor C allele of rs4818 (P=0.08), the low (A_C_C_G) (P=0.12) activity haplotypes and without H (G_C_G_G) activity haplotype carrier (P=0.11) tended to be slightly lower among PD patients. COMT gene haplotypes were strongly combined by rs6269 with rs4818, and rs4633 with rs4680, especially in PD patients. Homozygosis for the rs4633 (TT), rs4680 (AA) and of rs4633-rs4680 (TT/AA) were significantly more frequent in PD patients with ‘wearing-off’ phenomenon, longer disease duration and higher LED. Rs6267 (TT) was significantly associated with higher LED. Rs6269 (AA), rs4818 (CC) and rs6269-rs4818 (AA/CC) and without H (G_C_G_G) carrier associated with higher H&Y stage. Rs4633 (CC), rs4680 (GG), and rs4633-rs4680 (CC/GG) significantly associated with lower HAMD score (all P<0.05).

Conclusions: Our study showed a possible association of combined functional COMT haplotypes with PD susceptibility, and the combined COMT genotype also showed a possible influence in the motor response to levodopa, diseaseduration, ‘wearing-off’ phenomenon, daily LED and psychotic symptoms in PD patients, which may be useful in instituting individualized therapy for PD patients.

« Back to 2016 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/roles-of-combined-functional-catechol-o-methyltransferase-genotypes-in-chinese-parkinsons-disease-a-cross-sectional-survey/