Association of polymorphisms of the estrogen receptor gene with anxiety-related traits in children and adolescents: a longitudinal study.
Anxiety problems and associated temperamental traits are multifactorial, determined by the interaction of genetic and environmental factors. Genetic effects may involve both neurotransmitters and hormones. A good candidate gene for association with anxiety-related traits is the estrogen receptor (ESRalpha). Estrogen exerts an effect on mood and behavior in humans through gene regulation on binding to estrogen receptor protein. Association between ESRalpha polymorphism and anxiety-related traits was investigated in a cohort of 680 Australian adolescents studied from 4-8 months to 15-16 years of age. Genotype frequencies were estimated for polymorphic PvuII and XbaI restriction sites in intron 1 and a microsatellite [(TA)(n)] locus 5' of ESRalpha. There was strong linkage disequilibrium between the three loci and a significant sex difference was observed in allele (for (TA)(n), PvuII) and genotype (for XbaI) frequencies. There were no significant allelic or genotypic differences in anxiety-related traits for the three loci tested. However, some significant associations were found for PvuII/(TA)(n) and XbaI/(TA)(n) two-locus genotypes and anxiety, accounting for between 1.6% and 2.8% of the total variance for anxiety in this population. The discordance in Hardy-Weinberg proportions at the XbaI locus between the sexes is an important finding, perhaps indicating a sex-specific role for ESRalpha in fetal survival.
Prichard
Zoë
Z
John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Jorm
Anthony F
AF
Prior
Margot
M
Sanson
Ann
A
Smart
Diana
D
Zhang
Yafei
Y
Huttley
Gavin
G
Easteal
Simon
S
D000293:Adolescent; D000483:Alleles; D001007:Anxiety / Q000235:genetics* / Q000523:psychology; D002648:Child; D002653:Child Behavior Disorders / Q000235:genetics / Q000523:psychology; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D018900:Dinucleotide Repeats / Q000235:genetics; D047628:Estrogen Receptor alpha; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics*; D012737:Sex Factors
D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D004247:DNA