аЯрЁБс>ўџ -/ўџџџ,џџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџџьЅС7 №ПвbjbjUU .&7|7|в џџџџџџl$Є$ „ФФФФФФо ъŽ       $“ Г lД ђФФђђД 0ФФЩ 000ђтФФŽ 0ђŽ 0J0z z ФИ @ЄLЁХ$lдz z п 0 z ъFz 0$$йGENOTYPE ANALYSIS OF PLASMA DOPAMINE п-HYDROXYLASE IN PTSD M.Mustapic, Rudjer Boskovic Institute, Zagreb, Croatia D.Mueck-Seler, Rudjer Boskovic Institute, Zagreb, Croatia N.Pivac, Rudjer Boskovic Institute, Zagreb, Croatia D.Kozaric-Kovacic, Dubrava University Hospital, Zagreb, Croatia OBJECTIVES: Dopamine-beta-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine. Altered DBH activity has been reported in mood disorders. DBH activity can be measured in human plasma, where it exhibits genetically determined inter individual variability that is stabile within individuals over time. A recent study demonstrated a strong association between variance in plasma DBH activity and functional polymorphism (DBH-1021C(T) at the 5’ flanking region of the structural locus (DBH) encoding DBH protein. The aim of the present study was to investigate the DBH activity and allelic variation at DBH (DBH-1021C(T polymorphism) in war veterans with posttraumatic stress disorder (PTSD), to war veterans without PTSD and healthy controls. METHODS: Study included 88 male war veterans with PTSD, 17 male war veterans without PTSD and 79 male healthy controls. All subjects were drug free. The diagnosis of PTSD was made according to DSM-IV criteria. Plasma DBH activity was determined by a photometric method. Genotyping was performed using standard RFLP technique. RESULTS: The activity of plasma DBH was significantly higher in war veterans with PTSD as compared to enzyme activity in war veterans without PTSD. The T allele of the DBH-1021C(T polymorphism was significantly associated with lower DBH activity in all subjects. The significant difference in DBH activity between war veterans with and without PTSD did not corelate with the presence of –1021C(T polimorphism. Allelic frequencies in all groups did not deviate significantly from the Hardy-Weinberg equilibrium. (p>0,90 in all cases). CONCLUSIONS: Our preliminary data show that patients with PTSD have altered plasma DBH activity without a correlation with –1021C(T polymorphism. This finding could be explained with the chronic change in hypothalamic – pituitary adrenal axis activity, which can mediate diagnosis related, but –1021C(T independent, differences in plasma DBH activity. That can also be influenced by glucocorticoids acting on glucocorticoid response element (GRE) in DBH promotor, which can influence DBH transcription. Since DBH is a biochemical and genetic marker, this may reflect individual vulnerability to develop PTSD in the context of trauma. REFERENCES: Cubells JF, Kobayashi K, Nagatsu T, Kidd KK, Kidd JR, Calafell F, Kranzler HR, Ichinose H, Gelernter J (1997) Populationgenetics of a functional variant of the dopamine п-hydroxylase gene (DBH). Am J Med Genet 74:374–379 Cubells JF, Zabetian CP (2004) Human genetics of plasma dopamine п-hydroxylase activity: applications to research in psychiatry and neurology Psychopharmacology 174: 463-476 Hamner MB, Gold PB (1998) Plasma dopamine beta –hydroxylase activity in psychotic and non-psychotic post-traumatic stress disorder. Psychiat res 77:175-181 Nagatsu T, Udenfriend S (1972) Photometric assay of dopamine-п-hydroxylase activity in rat serum. Clin Chem 18:980–983 Zabetian CP, Anderson GM, Buxbaum SG, Elston RC, Ichinose H, Nagatsu T, Kim KS, Kim CH, Malison RT, GelernterJ, Cubells JF (2001) A quantitative-trait analysis of humanplasma-dopamine b-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus. Am J Hum Genet 68:515–522 <Grs‚Ќ­Жрсѓє!"#$/уфž$b j ѕ і   ь э y z † љьобШоМШоМШВМШЊљš}}ššШpШdШdШšX5CJOJQJ\^J j"№CJOJQJ^JB*CJOJQJ^Jph3fџ j"№CJOJQJ^JmH sH CJOJQJ^JmH sH 5CJOJQJ\^JmH sH H*OJQJ^JCJH*OJQJ^J6CJOJQJ]^JCJOJQJ^J6CJH*OJQJ]^J6@ˆ§џCJOJQJ]^J5>*CJOJQJ\^J OJQJ^J";<s­с!"#$b z ѕ прŽ+,ЄЅЮЯаб§ћћћћћћћћљѓљюљљћћћћћћћћћћћю$a$ ֠⧆ ћ ќ І Ї ѕ опЭЮЯавїыїыїлЮПЊПŽƒї<B*OJQJph<B*CJOJQJaJphB*CJOJQJaJph)B*CJOJPJQJ^JaJmH phsH B*CJOJQJ^JaJphCJOJQJ^JmH sH 5CJOJQJ\^JmH sH  j"№CJOJQJ^JCJOJQJ^Jбвњ$a$,1hА‚. 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