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Association between dopamine beta hydroxylase gene polymorphism and age at onset in male schizophrenia

Published online by Cambridge University Press:  24 June 2014

İ.Ö. Barlas ,
Umit Semiz ,
M.E. Erdal ,
Ayhan Algül ,
Ozlem I. Ay ,
M.A. Ateş ,
Handan Camdeviren ,
Cengiz Basoglu  and
Hasan Herken
İ.Ö. Barlas*
Affiliation:
Department of Medical Biology and Genetics, Medical Faculty of Mersin University, Mersin, Turkey
Umit Semiz
Affiliation:
Department of Psychiatry, GATA Haydarpasa Training Hospital, Istanbul, Turkey
M.E. Erdal
Affiliation:
Department of Medical Biology and Genetics, Medical Faculty of Mersin University, Mersin, Turkey
Ayhan Algül
Affiliation:
Department of Psychiatry, GATA Haydarpasa Training Hospital, Istanbul, Turkey
Ozlem I. Ay
Affiliation:
Department of Medical Biology and Genetics, Medical Faculty of Mersin University, Mersin, Turkey
M.A. Ateş
Affiliation:
Department of Psychiatry, GATA Haydarpasa Training Hospital, Istanbul, Turkey
Handan Camdeviren
Affiliation:
Department of Biostatistics, Medical Faculty of Duzce University, Düzce, Turkey
Cengiz Basoglu
Affiliation:
Department of Psychiatry, GATA Haydarpasa Training Hospital, Istanbul, Turkey
Hasan Herken
Affiliation:
Department of Psychiatry, Faculty of Medicine, Pamukkale University, Denizli, Turkey
*
I. Omer Barlas, Department of Medical Biology and Genetics, Medical Faculty of Mersin University, Yenisehir Kampusu, 33160 Mersin, Turkey. Tel: +903243412815/1071; Fax: +903243412400; E-mail: [email protected]
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Extract

Objectives: The heterogeneity of schizophrenia mainly results from variations in clinical expressions of the disease, such as age at onset, gender differences in onset of illness, symptoms and response to antipsychotic treatment. Enhanced sensitisation of dopamine pathways in males, having consistently an earlier onset, might be implicated as disease modifiers for schizophrenia in males.

Methods: In this study, we performed a case (n = 87)-control (n = 100) association study between the DBH5′-ins/del and DBH-444g/a polymorphisms of the DBH gene and also compared the level of psychotic symptoms between patients with different DBH genotypes/haplotypes with respect to antipsychotic therapeutic response and gender difference.

Results: No significant differences between allele and genotype and haplotype frequencies at either groups (p < 0.05). When the age is considered in patient group, a significant difference was observed between patients with ID genotype and with II genotype (p = 0.018). Patients with ID genotype have been diagnosed as schizophrenics in early ages when compared to II genotype carriers. We also found a significant difference between II and ID genotype (p = 0.007) when the gender had taken into account, showing that the ID genotype carriers had an early onset to schizophrenia.

Conclusions: This association was more significant in male schizophrenia patients than females. Thus, this finding may constitute a novel biological support for the prior finding that onset of schizophrenia varies with gender. The results also showed that critical genetic vulnerability may be associated with the presence or absence of the ID genotype of DBH5′-ins/del.

Keywords

age at onsetdopamine beta hydroxylasemale genderpolymorphismschizophrenia
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 3 , June 2012 , pp. 176 - 182
Copyright
Copyright © Cambridge University Press 2011

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References

1.Wei, J, Hai-Min, X, Ramchand, CN, Hemmings, GP.Is the polymorphic microsatellite repeat of the dopamine β-hydroxylase gene associated with biochemical variability of the catecholamine pathway in schizophrenia? Biol Psychiatry 1997;41:762–767.CrossRefGoogle ScholarPubMed
2.Gourion, D, Goldberger, C, Leroy, S et al. Age at onset of schizophrenia: interaction between brain-derived neurotrophic factor and dopamine D3 receptor gene variants. Neuroreport 2005;16:1407–1410.CrossRefGoogle ScholarPubMed
3.Leung, A, Chue, P.Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand Suppl 2000; 401:3–38.CrossRefGoogle ScholarPubMed
4.Lee, KY, Ahn, YM, Joo, EJ et al. Partial evidence of an association between epidermal growth factor A61G polymorphism and age at onset in male schizophrenia. Neurosci Res 2006;56:356–362.CrossRefGoogle ScholarPubMed
5.Arrufat, FJ, Dilevelsaz, R, Queralt, R et al. Analysis of the polymorphic (GT)(n) repeat at the dopamine beta-hydroxylase gene in Spanish patients affected by schizophrenia. Am J Med Genet 2000;96:88–92.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
6.Jonsson, EG, Jamra, RA, Schumacher, J et al. No association between a putative functional promoter variant in the dopamine b-hydroxylase gene and schizophrenia. Psychiatr Genet 2003;13:175–178.CrossRefGoogle Scholar
7.Cubells, JF, van Kammen, DP, Kelley, ME et al. Dopamine beta-hydroxylase: two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation. Hum Genet 1998;102:533–540.CrossRefGoogle ScholarPubMed
8.Williams, HJ, Bray, N, Murphy, KC et al. No evidence for association between schizophrenia and a functional variant of the human dopamine beta hydroxylase gene (DBH). Am J Med Genet 1999;88:557–559.3.0.CO;2-F>CrossRefGoogle Scholar
9.Yamamoto, K, Cubells, JF, Gelernter, J et al. Dopamine beta-hydroxylase (DBH) gene and schizophrenia phenotypic variability: a genetic association study. Am J Med Genet B 2003;117B:33–38.CrossRefGoogle ScholarPubMed
10.Crow, TJ.The two-syndrome concept: origins and current status. Schizophr Bull 1985;11:471–486.CrossRefGoogle ScholarPubMed
11.Park, JK, Kim, JW, Lee, HJ et al. Dopamine beta-hydroxylase gene polymorphisms and psychotic symptoms in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2007;144B:944–945.CrossRefGoogle ScholarPubMed
12.DeLisi, LE, Wise, CD, Potkin, SG et al. Dopamine-beta-hydroxylase, monoamine oxidase, and schizophrenia. Biol Psychiatry 1980;15:895–907.Google ScholarPubMed
13.Meltzer, HY, Nasr, SJ, Tong, C.Serum dopamine-β-hydroxylase in schizophrenia. Biol Psychiatry 1980;15:781–788.Google ScholarPubMed
14.Meszaros, K, Lenzinger, E, Fureder, T et al. Schizophrenia and the dopamine-beta hydroxylase gene: results of a linkage and association study. Psychiatr Genet 1996;6:17–22.CrossRefGoogle ScholarPubMed
15.Cho, AR, Park, JK, Kim, JW et al. An association study between four polymorphisms in the dopamine beta-hydroxylase gene and schizophrenia in Korean population. J Korean Soc Biol Ther Psychiatry 2007;13:1.Google Scholar
16.Arató, M, Bagdy, G, Blümel, F et al. Reduced serum dopamine-beta hydroxylase activity in paranoid schizophrenics. Pharmacopsychiatria 1983;16:19–22.CrossRefGoogle ScholarPubMed
17.Sternberg, DE, van Kammen, DP, Lerner, P et al. CSF dopamine-β-hydroxylase in schizophrenia: low activity associated with good prognosis and good response to neuroleptic treatment. Arch Gen Psychiatry 1983;40:743–747.CrossRefGoogle Scholar
18.Van Kammen, DP, Kelley, ME, Gilbertson, MW et al. CSF dopamine β hydroxylase in schizophrenia: associations with premorbid functioning and brain computerized tomography scan measures. Am J Psychiatry 1994;151:372–378.Google ScholarPubMed
19.Wood, JG, Joyce, PR, Miller, AL et al. A polymorphism in the dopamine beta-hydroxylase gene is associated with “paranoid ideation” in patients with major depression. Biol Psychiatry 2002;51:365–369.CrossRefGoogle ScholarPubMed
20.Cubells, JF, Kranzler, HR, McCance-Katz, E et al. Haplotype at the DBH locus, associated with low plasma dopamine beta hydroxylase activity, also associates with cocaine-induced paranoia. Mol Psychiatry 2000;5:56–63.CrossRefGoogle ScholarPubMed
21.Köhnke, MD, Kolb, W, Köhnke, AM et al. DBH_444G/A polymorphism of the dopamine b-hydroxylase gene is associated with alcoholism but not with severe alcohol withdrawal symptoms. J Neural Transm 2006;113:869–876.CrossRefGoogle Scholar
22.Thompson, Jl, Pogue-Geile, MF, Grace, AA.Developmental pathology, dopamine, and stress: a model for the age of onset of schizophrenia symptoms. Schizophr Bull 2004; 30:875–900.CrossRefGoogle Scholar
23.de Chalde'e, M, Laurent, C, Thibaut, F et al. Linkage disequilibrium on the COMT gene in French schizophrenics and controls. Am J Med Genet B 1999;88:452–457.3.0.CO;2-0>CrossRefGoogle Scholar
24.Kremer, I, Rietschel, M, Dobrusin, M et al. No association between the dopamine D3 receptor Bal I polymorphism and schizophrenia in a family-based study of a Palestinian Arab population. Am J Med Genet B 2000;96:778–780.3.0.CO;2-2>CrossRefGoogle Scholar
25.Hong, CJ, Yu, YWY, Lin, CH et al. An association study of a brain-derived neurotrophic factor Val66Met polymorphism and clozapine response of schizophrenic patients. Neurosci Lett 2003;349:206–208.CrossRefGoogle ScholarPubMed
26.Yue, W, Liu, Z, Kang, G et al. Association of G72/G30 polymorphisms with early-onset and male schizophrenia. Neuroreport 2006;17:1899–1902.CrossRefGoogle ScholarPubMed
27.Hanninen, K, Katila, H, Anttila, S et al. Epidermal growth factor a61g polymorphism is associated with the age of onset of schizophrenia in male patients. J Psychiatr Res 2007;4:8–14.CrossRefGoogle Scholar
28.Overall, JE, Gorham, DE.The brief psychiatric rating scale. Psychol Rep 1962;10:812.CrossRefGoogle Scholar
29.Andreasen, NC.The scale for the assessment of positive symptoms (SAPS). Iowa City, IA: The University of Iowa, 1984.Google Scholar
30.Andreasen, NC.The scale for the assessment of negative symptoms (SANS). Iowa City, IA: The University of Iowa, 1983.Google Scholar
31.Kumra, S, Kranzler, H, Gerbino-Rosen, G et al. Clozapine and “high-dose” olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison. Biol Psychiatry 2008;63:524–529.CrossRefGoogle ScholarPubMed
32.Miller, SA, Dykes, DD, Polesky, HF.A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.CrossRefGoogle ScholarPubMed
33.Van Kammen, DP, Mann, LS, Sternberg, DE et al. Dopamine-beta-hydroxylase activity and homovanillic acid in spinal fluid of schizophrenics with brain atrophy. Science 1983;220:974–977.CrossRefGoogle ScholarPubMed
34.Wei, J, Ramchand, CN, Hemmings, GP.Possible control of dopamine beta-hydroxylase via a codominant mechanism associated with the polymorphic (GT)n repeat at its gene locus in healthy individuals. Hum Genet 1997;99:52–55.CrossRefGoogle Scholar
35.Sapru, MK, Rao, BS, Channabasavanna, SM.Serum dopamine-beta-hydroxylase activity in clinical subtypes of depression. Acta Psychiatr Scand 1989;80:474–478.CrossRefGoogle ScholarPubMed
36.Cubells, JF, Price, LH, Meyers, BS et al. Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression. Biol Psychiatry 2002;51:358–364.CrossRefGoogle ScholarPubMed
37.Cubells, JF, Zabetian, CP.Human genetics of plasma dopamine β-hydroxylase activity: applications to research in psychiatry and neurology. Psychopharmacology 2004;174:463–476.CrossRefGoogle ScholarPubMed
38.Kalayasiri, R, Sughondhabirom, A, Gueorguieva, R et al. Dopamine beta-hydroxylase gene (DBH) -1021C/T influences self-reported paranoia during cocaine self-administration. Biol Psychiatry 2007;61:1310–1313.CrossRefGoogle Scholar
39.Szymanski, S, Lieberman, JA, Alvir, JM et al. Gender differences in onset of illness, treatment response, course, and biologic indexes in first-episode schizophrenic patients. Am J Psychiatry 1995;152:698–703.Google ScholarPubMed
40.Salem, JE, Kring, AM.The role of gender differences in the reduction of etologic heterogeneity in schizophrenia. Clin Psychol Rev 1998;18:795–819.CrossRefGoogle Scholar
41.Rao, ML, Kölsch, H.Effects of estrogen on brain development and neuroprotection implications for negative symptoms in schizophrenia. Psychoneuroendocrinology 2003;28:83–96.CrossRefGoogle ScholarPubMed