Impact of COMT H108L, MAOB int 13 A>G and DRD2 haplotype on the susceptibility to Parkinson's disease in South Indian subjects.
In view of documented evidence demonstrating the association of dopaminergic metabolism and neurotransmission with Parkinson's disease (PD), a case-control study was conducted to investigate the impact of particular polymorphisms in the catechol O-methyl transferase (COMT) H108L, monoamine oxidase B (MAOB) int 13 A>G, dopamine transporter 1 (DAT1) A1215G, dopamine receptor D2 (DRD2) Taq1A, DRD2 Taq1B and DRD2 Taq1D genes on the susceptibility to PD. PCR-RFLP method was used for the genetic analysis. The COMT H108L polymorphism increased PD risk by 1.4-fold (95%CI: 1.02-1.98), whereas reduced risk was observed with MAOB int 13 A>G polymorphism (OR: 0.77, 95%CI: 0.51-0.99). Multifactor dimensionality reduction analysis showed gene-gene interactions between these two loci that resulted in loss of the protective role of MAOB G-allele in the presence of COMT L-allele. DAT1A1215G polymorphism in the exon 9 was not associated with PD. Individually, DRD2 polymorphisms showed null association. However, all-variant haplotype of DRD2 locus i.e. T-G-T haplotype showed 29.8-fold risk for PD compared to all-wild haplotype i.e., C-A-C haplotype (95%CI: 6.85-130.4). To conclude, genetic variants of COMT, MAOB and DRD2 loci modulate susceptibility to PD in South Indian subjects.
Nadella
N
Kumudini
Addepally
A
Umai
Yalavarthy Prameela
YP
Devi
Shaik Mohammad
SM
Naushad
Rukmini
R
Mridula
Rupam
R
Borgohain
Vijay Kumar
VK
Kutala
D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*
C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase