Paraoxonase 1 promoter and coding region polymorphisms in Parkinson’s disease

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 74; no. 4; pp. 546 - 547
• Main Authors: Kelada, S N, Costa-Mallen, P, Checkoway, H, Viernes, H A, Farin, F M, Smith-Weller, T, Franklin, G M, Costa, L G, Longstreth, W T, Furlong, C E, Jarvik, G P, Swanson, P D
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01-04-2003; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adult; Age; Aged; Aged, 80 and over; Aryldialkylphosphatase; Confidence intervals; Enzymes; epidemiology; Esterases - genetics; Ethnicity; Female; Genes; Haplotypes; Health risk assessment; Humans; Letter; Male; Middle Aged; Open Reading Frames - genetics; paraoxonase; Parkinson Disease - genetics; Parkinson's disease; Pesticides; Polymorphism, Genetic - genetics; Promoter Regions, Genetic - genetics; Studies
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.74.4.546

The leucine (L) to methionine (M) substitution at codon 55 does not affect the catalytic efficiency of substrate hydrolysis by the enzyme, but the PON1 55M allele is correlated with decreased mRNA and protein levels, because of linkage disequilibrium with a single nucleotide polymorphism (SNP) at position -108 of the promoter region of the gene. A significant association of the 192R allele with PD was found in a population of patients of Japanese ethnicity with comparatively low mean age of onset. 1 In contrast, no difference in genotypes distributions was found between PD cases and controls for the PON1 Q192R polymorphism in an Australian study 2 nor in another study on subjects of Russian ethnicity. 3 In a more recent study by Akhmedova et al 4 on the same Russian population, the M55 allele was found to be associated with PD. No associations for the amino acid codon 55 and 192 polymorphisms were found in a study from China. 5 In this study, we examined associations of two promoter (G-162A and C-108T) and two coding region (M55L and Q192R) polymorphisms in PON1 with PD. Newly diagnosed idiopathic PD patients (n=150; 91 men and 59 women), aged 37 to 88 years, were identified by neurology and general medical practice clinics of the group health cooperative (GHC) from the Puget Sound area in western Washington State.