Decreased serum arylesterase activity in autism spectrum disorders.
The PON1 gene, previously found associated with autism spectrum disorders (ASDs), encodes a serum protein responsible for the detoxification of organophosphates (OPs) and able to exert several enzymatic activities. PON1 arylesterase, but not diazoxonase activity, was significantly decreased in 174 ASD patients compared to 175 first-degree relatives and 144 controls (P=2.65×10⁻¹⁶). First degree relatives displayed intermediate activities, closer to patient than to control levels. Differences between patients, first-degree relatives and controls were especially evident among 164 Italians compared to 329 Caucasian-Americans, because arylesterase activity was significantly higher in Italian controls, compared to Caucasian-American controls (P=2.84×10⁻¹⁶). Arylesterase activity and PON protein concentrations were not significantly correlated, supporting a functional inhibition of arylesterase activity in ASD patients over quantitative changes in protein amounts. Serum arylesterase activity, in combination with PON1 genotypes at two single nucleotide polymorphisms (SNPs) known to influence protein amounts (rs705379: C-108T) and substrate specificity (rs662: Q192R), was able to discriminate ASD patients from controls with elevated sensitivity and specificity, depending on genotype and ethnic group. Serum arylesterase activity and genotyping at these two SNPs could thus represent an informative biochemical/genetic test, able to aid clinicians in estimating autism risk in ethnic groups with higher baseline arylesterase activity levels.
Gaita
Laura
L
Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Rome, Italy.
Manzi
Barbara
B
Sacco
Roberto
R
Lintas
Carla
C
Altieri
Laura
L
Lombardi
Federica
F
Pawlowski
Tracy L
TL
Redman
Margot
M
Craig
David W
DW
Huentelman
Matthew J
MJ
Ober-Reynolds
Sharman
S
Brautigam
Sarah
S
Melmed
Raun
R
Smith
Christopher J
CJ
Marsillach
Judith
J
Camps
Jordi
J
Curatolo
Paolo
P
Persico
Antonio M
AM
D000293:Adolescent; D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000097:blood*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000097:blood* / Q000208:ethnology* / Q000235:genetics; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005190:Family; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007558:Italy / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018709:Statistics, Nonparametric; D044465:White People / Q000235:genetics; D055815:Young Adult
D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human