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|Title:||The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinsons disease, levodopa treatment response, and complications||Authors:||Bialecka M.
Single nucleotide polymorphisms
|Issue Date:||2008||Publisher:||Lippincott, Williams & Wilkins||Citation:||Bialecka M., Kurzawski M., Klodowska-Duda G., Opala G., Tan E.-K., Drozdzik M. (2008). The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinsons disease, levodopa treatment response, and complications. Pharmacogenetics and Genomics 18 (9) : 815-821. ScholarBank@NUS Repository. https://doi.org/10.1097/FPC.0b013e328306c2f2||Abstract:||INTRODUCTION: Differences in catechol-O-methyltransferase (COMT) activity and genotype may determine individual variations in the therapeutic response to levodopa or Parkinsons disease (PD) susceptibility. The role of functional COMT haplotypes in PD susceptibility and treatment response has not been examined. OBJECTIVES: In this case "control study, we investigated the association of the most common COMT gene haplotypes (formed by single nucleotide polymorphisms (SNPs): rs6269:A>G; rs4633C>T; rs4818:C>G; and rs4680:A>G) with PD risk and the association of the COMT haplotypes with the dose and complications of levodopa therapy in PD patients. METHODS: A total of 679 study participants (322 PD and 357 controls) were included. Each participant was genotyped for four SNPs in the COMT gene, located in a common haploblock, that has been shown to influence COMT enzymatic activity. The influence of COMT haplotypes on the dose of levodopa administered during fifth year of treatment, and occurrence of motor complications were examined in PD patients. The EH program (Jurg Ott, Rockefeller University, New York, USA) was used to estimate haplotype frequencies. RESULTS: The estimated frequencies of low (A-C-C-G) and medium (A-T-C-A) activity haplotypes tended to be slightly lower among PD patients when compared with controls (P?0.09, G-C-G-G-high activity haplotype as reference). The frequency of G-C-G-G (high activity) haplotype carriers was higher in late onset PD patients (P?0.04) compared with controls. The mean levodopa dose increased with the activity of the functional haplotypes (low||Source Title: ||Pharmacogenetics and Genomics
||Appears in Collections:||Staff Publications|
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