title: Influence of catechol-O-methyltransferase Val158Met polymorphism on startle response in the presence of high estradiol levels.
abstract: BACKGROUND
  both human and animal studies have shown a somewhat complex COMT-by-sex interaction effect on brain function and dysfunction. A functional variation in the gene coding for the catechol-O-methyltransferase (COMT) enzyme, which metabolizes dopamine and noradrenaline, has been related to executive and emotional functions, and to sex dimorphism.
  
  
  OBJECTIVE
  to investigate if COMT Val158Met genotype influences startle response in pregnant women, given their physiologically elevated estradiol levels.
  
  
  METHODS
  seventy-three pregnant women were assessed in gestational week 38 for acoustic startle response, measured by electromyography of the blink reflex, during control condition, positive and negative anticipation stimuli, and pleasant and unpleasant image stimuli. A blood sample was taken for measurement of estradiol levels and genetic analysis.
  
  
  RESULTS
  the results indicated a COMT Val158Met effect on startle response across all conditions (main effect of genotype, F(2,70=3.58), p=0.033), where Val/Val women displayed higher startle magnitudes than Val/Met carriers (Cohen's d=0.71). No significant difference by genotype was found in affective modulation. The findings also suggested an estrogen dose-dependent effect of COMT Val158Met on startle reflex. Among women with higher pregnancy-induced estradiol levels, Val/Val carriers had markedly higher startle response across conditions than heterozygotes (Cohen's d=1.36; F(4,21=11.07); p=0.003), while this effect was not present in women with estradiol levels under the median concentration.
  
  
  CONCLUSIONS
  the observed effect of COMT Val158Met by estradiol on overall startle response is likely to be due to a variable noradrenergic transmission depending on COMT activity in a possible interaction with estradiol.
authors: Department of Neuroscience, Unit of Pharmacology, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden. erika.comasco@neuro.uu.se
authors: Erika
authors: E
authors: Comasco
authors: Charlotte
authors: C
authors: Hellgren
authors: Inger
authors: I
authors: Sundström-Poromaa
mesh_terms: D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000502:physiology*; D004644:Emotions / Q000502:physiology; D004958:Estradiol / Q000097:blood / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011247:Pregnancy; D013216:Reflex, Startle / Q000235:genetics / Q000502:physiology*
chemical_list: D004958:Estradiol; D002394:Catechol O-Methyltransferase