engleski

Associations of the DBH gene with plasma dopamine beta-hydroxylase activity in Alzheimer's disease

Alzheimer’ s disease (AD) is complex and polygenic disorder. Polymorphisms within the dopamine beta-hydroxylase (DBH) gene could contribute to etiology of Alzheimer’ s disease (AD), given the well-documented changes in the catecholamine-mediated neurotransmission that occurs in this disorder. The aim of the present study was to investigate two DBH gene polymorphisms (rs 1611115 and rs6271) and plasma DBH activity in patients with AD and healthy controls. The study included 254 patients (mean ± ; SD age 78.1 ± ; 10.6 years ; MMSE = 13.9 ± ; 11.9) with AD (NINCDS-ADRDA and DSM-IV-TR criteria) and 188 healthy controls (74.2 ± ; 8.8 years). Plasma DBH activity was determined by a photometric method by Nagatsu and Udenfriend and DBH genotype with TaqMan Real-time allelic discrimination technique after extraction of DNA from whole blood with salting out procedure. A significantly (F= 19.1, df=1, p=0.0002 ; ANOVA) lower plasma DBH activity was found in AD patients (9.38± ; 6.15 IU/l) compared to healthy controls (16.19± ; 11.95 IU/l). There was a significant difference in plasma DBH activity (F=22.5, df=1 ; p<0.0001) between different genotypes. Distribution of genotypes and alleles of DBH polymorphism rs1611115 did not differ significantly between AD and control samples ( 2=0.12, df=2, p=0.941 and  2=0.01, df=1, p=0.920, respectively). There were also, no significant differences in genotype and allele distributions of the other DBH polymorphism rs6271 ( 2=2.56, df=2, p=0.278 and  2=0.61, df=1, p=0.435) between groups. Two tested polymorphisms of DBH were not in the linkage disequilibrium (  2= 2.45, df=1, p =0.117). Interaction tested between the two independent factors (diagnosis x genotype) gave no significant (F=0.70, df=2, p=0.499) difference in plasma DBH activity. Our study did not provide evidence for association of two DBH genetic polymorphisms with AD. The results show significantly lower DBH activity in AD and therefore genotype-controlled measurement of plasma DBH activity might be used as a potential biological marker in AD.

DBH gene; plasma dopamine beta-hydroxylase activity; Alzheimer's disease

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