Analysis of the polymorphic (GT)n repeat at the dopamine ?-hydroxylase gene in Spanish patients affected by schizophrenia

Abstract

The presence of a polymorphic (GT)(n) repeat, a microsatellite repeat, at the human dopamine beta-hydroxylase (DBH) gene had been previously investigated in healthy people and in schizophrenic patients. The different DBH genotypes had been found to be associated to different DBH biochemical function, but no differences were found in the allelic and genotype frequencies between schizophrenic and control groups. To further clarify the potential involvement of the variation at the DBH gene in schizophrenia we have studied the DBH (GT)(n) repeat in a sample of 47 Spanish schizophrenic patients, in their healthy relatives (n = 72), and in a control population (n = 74). We have been able to identify five different variants of the DBH gene (A1, A2, A3, A4, A5) in the different groups. Subsequent statistical analysis revealed that the genotypes as well as the allele frequencies did not differ significantly among schizophrenic patients and the control population. Interestingly, the allelic variant A2 and the genotype A4/A2 were significantly more frequent in schizophrenic patients as compared with their healthy relatives. However, the association of the A2 allele with schizophrenia was not supported by the haplotype relative risk analysis of transmitted versus nontransmitted alleles. Therefore, although it will be important to extend the present analysis in a larger sample of schizophrenic patients and controls, our results suggest that the (GT)(n) does not seem to play a major role in the genetics of schizophrenia at least in this group of Spanish schizophrenic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:88-92, 2000.

Normal values of CD4 and CD8 lymphocyte subsets in healthy indian adults and the effects of sex, age, ethnicity, and smoking

“…In this study, no differences in allelic or in the haplotype frequencies of the DBH5′‐Ins/del and DBH 444 g/a polymorphims of the DBH gene were observed between schizophrenic patients and normal controls. These results are consistent with several studies investigating markers located in the close vicinity [Meszaros et al, 1996], the coding (Ala304Ser) [Williams et al, 1999] and 5′ untranslated regions (polymorphic (GT)n repeat) [Arrufat et al, 2000] of the DBH gene, which failed to show either linkage to or association with schizophrenia. Overall, these results suggest that the DBH gene does not play a causative role in schizophrenia.…”

Human genetics of plasma dopamine ?-hydroxylase activity: applications to research in psychiatry and neurology

“…However, studies employing operational diagnostic criteria for schizophrenia have found no difference between either the serum or CSF DBH activities of patients and controls (Meltzer et al 1976(Meltzer et al , 1980Sternberg et al 1982Sternberg et al , 1983van Kammen et al 1994). Several genetic association studies, examining a variety of polymorphisms at DBH, have found no evidence for associations to schizophrenia (Meszaros et al 1996;Wei et al 1997b;Williams et al 1999;Arrufat et al 2000). Thus, it is now clear that neither plasma DβH levels nor genotypes at DBH distinguish schizophrenic patients from healthy individuals.…”

Association of the dopamine β‐hydroxylase 19 bp insertion/deletion polymorphism with positive symptoms but not tardive dyskinesia in schizophrenia

“…Two studies of multiplex families affected with schizophrenia reported modest positive linkage scores in this region (Riley et al ., ; Kaufmann et al ., ), whereas an Austrian research team, directly assessing the DBH locus, did not find evidence for linkage (Meszaros et al ., ). Little evidence for association between DBH variants and schizophrenia has been reported (Wei et al ., , ; Williams et al ., ; Arrufat et al ., ; Jonsson et al ., ; Park et al ., ), but the DBH gene may be involved with the emergence of psychotic symptoms in schizophrenia or in cocaine induced paranoia (Cubells et al ., ; Yamamoto et al ., ). More recently, Park et al .…”