Paraoxonase 1 activities and polymorphisms in autism spectrum disorders.
Autism spectrum disorders (ASD) comprise a complex and heterogeneous group of conditions of unknown aetiology, characterized by significant disturbances in social, communicative and behavioural functioning. Recent studies suggested a possible implication of the high-density lipoprotein associated esterase/lactonase paraoxonase 1 (PON1) in ASD. In the present study, we aimed at investigating the PON1 status in a group of 50 children with ASD as compared to healthy age and sex matched control participants. We evaluated PON1 bioavailability (i.e. arylesterase activity) and catalytic activity (i.e. paraoxonase activity) in plasma using spectrophotometric methods and the two common polymorphisms in the PON1 coding region (Q192R, L55M) by employing Light Cycler real-time PCR. We found that both PON1 arylesterase and PON1 paraoxonase activities were decreased in autistic patients (respectively, P < 0.001, P < 0.05), but no association with less active variants of the PON1 gene was found. The PON1 phenotype, inferred from the two-dimensional enzyme analysis, had a similar distribution in the ASD group and the control group. In conclusion, both the bioavailability and the catalytic activity of PON1 are impaired in ASD, despite no association with the Q192R and L55M polymorphisms in the PON1 gene and a normal distribution of the PON1 phenotype.
Paşca
Sergiu P
SP
Department of Medical Biochemistry, Faculty of Medicine, Iuliu HaTieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Dronca
Eleonora
E
Nemeş
Bogdan
B
Kaucsár
Tamás
T
Endreffy
Emõke
E
Iftene
Felicia
F
Benga
Ileana
I
Cornean
Rodica
R
Dronca
Maria
M
D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D001321:Autistic Disorder / Q000201:enzymology* / Q000235:genetics; D002648:Child; D057075:Enzyme Assays; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human