title: Acetylcholinesterase/paraoxonase genotype and expression predict anxiety scores in Health, Risk Factors, Exercise Training, and Genetics study.
abstract: Anxiety involves complex, incompletely understood interactions of genomic, environmental, and experience-derived factors, and is currently being measured by psychological criteria. Here, we report previously nonperceived interrelationships between expression variations and nucleotide polymorphisms of the chromosome 7q21-22 acetylcholinesterase-paraoxonase 1 (ACHE-PON1) locus with the trait- and state-anxiety measures of 461 healthy subjects from the Health, Risk Factors, Exercise Training, and Genetics Family Study. The AChE protein controls the termination of the stress-enhanced acetylcholine signaling, whereas the PON protein displays peroxidase-like activity, thus protecting blood proteins from oxidative stress damages. Serum AChE and PON enzyme activities were both found to be affected by demographic parameters, and showed inverse, reciprocal associations with anxiety measures. Moreover, the transient scores of state anxiety and the susceptibility score of trait anxiety both appeared to be linked to enzyme activities. This finding supported the notion of corresponding gene expression relationships. Parallel polymorphisms in the ACHE and PON1 genes displayed apparent associations with both trait- and state-anxiety scores. Our findings indicate that a significant source of anxiety feelings involves inherited and acquired parameters of acetylcholine regulation that can be readily quantified, which can help explaining part of the human variance for state and trait anxiety.
authors.affiliation: Department of Biological Chemistry, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Ella H
authors.initials: EH
authors.lastname: Sklan
authors.forename: Alexander
authors.initials: A
authors.lastname: Lowenthal
authors.forename: Mira
authors.initials: M
authors.lastname: Korner
authors.forename: Ya'acov
authors.initials: Y
authors.lastname: Ritov
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Landers
authors.forename: Tuomo
authors.initials: T
authors.lastname: Rankinen
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Leon
authors.forename: Treva
authors.initials: T
authors.lastname: Rice
authors.forename: D C
authors.initials: DC
authors.lastname: Rao
authors.forename: Jack H
authors.initials: JH
authors.lastname: Wilmore
authors.forename: James S
authors.initials: JS
authors.lastname: Skinner
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
mesh_terms: D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D000367:Age Factors; D001007:Anxiety / Q000201:enzymology* / Q000235:genetics*; D043303:Aryldialkylphosphatase / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D001483:Base Sequence; D015992:Body Mass Index; D002091:Butyrylcholinesterase / Q000097:blood; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D015331:Cohort Studies; D015444:Exercise / Q000502:physiology; D005192:Family Health; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D043303:Aryldialkylphosphatase