Iranian Journal of Psychiatry 2016. 11(4):239-243.

Lack of Association between Dopamine Beta-Hydroxylase (DBH) 19-bp Insertion/Deletion Polymorphism and Risk of Schizophrenia
Mansour shakiba, Mohammad Hashemi, Sara Shahrabadi, Maryam Rezaei, Mohsen Taheri


Objective: Interaction between genetic and environmental factors is considered as major factors in Schizophrenia (SCZ). It has been shown that dopaminergic and noradrenergic neurotransmission dysfunction play an essential role in the SCZ pathogenesis.

This study aimed to find the impact of functional 19-bp insertion/deletion (ins/del) polymorphism in dopamine beta-hydroxylase (DBH) gene on SCZ risk in a sample of Iranian population.

Method: This case-control study was conducted on 109 SCZ patients and 116 matched healthy subjects. Genomic DNA samples were extracted from peripheral blood cells using salting out method. Genotyping of 19-bp ins/del DBH polymorphism was done using Polymerase Chain Reaction (PCR) method.

Results: Neither the overall chi-square comparison of cases and controls (


Deletion; Dopamine Beta-Hydroxylase; Insertion; Polymorphism; Schizophrenia

Full Text:



Hui L, Zhang X, Huang XF, Han M, Fernandez F, Yu Y, et al. The dopamine b-hydroxylase 19 bp insertion/deletion polymorphism was associated with first-episode but not medicated chronic schizophrenia. J Psychiatr Res 2012; 46: 733-737.

Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med 2005; 2: e141.

Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003; 60: 1187-1192.

Ishiguro H, Kim KT, Joh TH, Kim KS. Neuron-specific expression of the human dopamine beta-hydroxylase gene requires both the cAMP-response element and a silencer region. J Biol Chem 1993; 268: 17987-17994.

Schank JR, Ventura R, Puglisi-Allegra S, Alcaro A, Cole CD, Liles LC, et al. Dopamine beta-hydroxylase knockout mice have alterations in dopamine signaling and are hypersensitive to cocaine. Neuropsychopharmacology 2006; 31: 2221-2230.

Davis J, Moylan S, Harvey BH, Maes M, Berk M. Neuroprogression in schizophrenia: Pathways underpinning clinical staging and therapeutic corollaries. Aust N Z J Psychiatry 2014; 48: 512-529.

Fan H, Zhang F, Xu Y, Huang X, Sun G, Song Y, et al. An association study of DRD2 gene polymorphisms with schizophrenia in a Chinese Han population. Neurosci Lett 2010; 477: 53-56.

Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version III--the final common pathway. Schizophr Bull 2009; 35: 549-562.

Solismaa A, Kampman O, Seppala N, Viikki M, Makela KM, Mononen N, et al. Polymorphism in alpha 2A adrenergic receptor gene is associated with sialorrhea in schizophrenia patients on clozapine treatment. Hum Psychopharmacol 2014; 29: 336-341.

Sorgi PJ, Ratey JJ, Polakoff S. Beta-adrenergic blockers for the control of aggressive behaviors in patients with chronic schizophrenia. Am J Psychiatry 1986; 143: 775-776.

Arnsten AF. Adrenergic targets for the treatment of cognitive deficits in schizophrenia. Psychopharmacology (Berl) 2004; 174: 25-31.

Perry SE, Summar ML, Phillips JA, 3rd, Robertson D. Linkage analysis of the human dopamine beta-hydroxylase gene. Genomics 1991; 10: 493-495.

Dunnette J, Weinshilboum R. Human serum dopamine beta-hydroxylase: correlation of enzymatic activity with immunoreactive protein in genetically defined samples. Am J Hum Genet 1976; 28: 155-166.

Wilson AF, Elston RC, Siervogel RM, Tran LD. Linkage of a gene regulating dopamine-beta-hydroxylase activity and the ABO blood group locus. Am J Hum Genet 1988; 42: 160-166.

Cubells JF, Sun X, Li W, Bonsall RW, McGrath JA, Avramopoulos D, et al. Linkage analysis of plasma dopamine beta-hydroxylase activity in families of patients with schizophrenia. Hum Genet 2011; 130: 635-643.

Cubells JF, van Kammen DP, Kelley ME, Anderson GM, O'Connor DT, Price LH, 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.

Cubells JF, Kranzler HR, McCance-Katz E, Anderson GM, Malison RT, Price LH, et al. A 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.

Cubells JF, Zabetian CP. Human genetics of plasma dopamine beta-hydroxylase activity: applications to research in psychiatry and neurology. Psychopharmacology (Berl) 2004; 174: 463-476.

Tang YL, Epstein MP, Anderson GM, Zabetian CP, Cubells JF. Genotypic and haplotypic associations of the DBH gene with plasma dopamine beta-hydroxylase activity in African Americans. Eur J Hum Genet 2007; 15: 878-883.

Hui L, Han M, Huang XF, Ye MJ, Zheng K, He JC, et al. Possible association between DBH 19 bp insertion/deletion polymorphism and clinical symptoms in schizophrenia with tardive dyskinesia. J Neural Transm (Vienna) 2015; 122: 907-914.

Zhou N, Yu Q, Li X, Yu Y, Kou C, Li W, et al. Association of the dopamine beta-hydroxylase 19 bp insertion/deletion polymorphism with positive symptoms but not tardive dyskinesia in schizophrenia. Hum Psychopharmacol 2013; 28: 230-237.

Yamamoto K, Cubells JF, Gelernter J, Benkelfat C, Lalonde P, Bloom D, et al. Dopamine beta-hydroxylase (DBH) gene and schizophrenia phenotypic variability: a genetic association study. Am J Med Genet B Neuropsychiatr Genet 2003; 117b: 33-38.

Barlas IO, Semiz U, Erdal ME, Algul A, Ay OI, Ates MA, et al. Association between dopamine beta hydroxylase gene

polymorphism and age at onset in male schizophrenia. Acta Neuropsychiatr 2012; 24: 176-182.

Hashemi M, Moazeni-Roodi AK, Fazaeli A, Sandoughi M, Bardestani GR, Kordi-Tamandani DM, et al. Lack of association between paraoxonase-1 Q192R polymorphism and rheumatoid arthritis in southeast Iran. Genet Mol Res 2010; 9: 333-339.

Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 1991; 148: 1474-1486.

Srivastava V, Deshpande SN, Thelma BK. Dopaminergic pathway gene polymorphisms and genetic susceptibility to schizophrenia among north Indians. Neuropsychobiology 2010; 61: 64-70.

Dai D, Wang Y, Yuan J, Zhou X, Jiang D, Li J, et al. Meta-analyses of 10 polymorphisms associated with the risk of schizophrenia. Biomed Rep 2014; 2: 729-736.

Hui L, Han M, Huang XF, Ye MJ, Zhang X, He JC, et al. Association between DbetaH 5'-insertion/deletion polymorphism and cognition in patients with chronic schizophrenia. J Clin Psychiatry 2016; 77: 379-385.

Hui L, Zhang X, Huang XF, Han M, Fernandez F, Yu Y, et al. The dopamine b-hydroxylase 19 bp insertion/deletion polymorphism was associated with first-episode but not medicated chronic schizophrenia. J Psychiatr Res 2012; 46: 733-737.

Weinshilboum RM. Human biochemical genetics of plasma dopamine-beta-hydroxylase and erythrocyte catechol-o-methyltransferase. Hum Genet Suppl 1978: 101-112.

Kemper CM, O'Connor DT, Westlund KN. Immunocytochemical localization of dopamine-beta-hydroxylase in neurons of the human brain stem. Neuroscience 1987; 23: 981-989.

Hui L, Zhang X, Yu YQ, Han M, Huang XF, Chen DC, et al. Association between DBH 19 bp insertion/deletion polymorphism and cognition in first-episode schizophrenic patients. Schizophr Res 2013; 147: 236-240.

Long J, Huang G, Liang B, Ling W, Guo X, Jiang J, et al. The dopamine beta-hydroxylase gene polymorphism rs1611114 is associated with schizophrenia in the Chinese Zhuang but not Chinese Han population. Mol Genet Genomics 2016; 291: 1813-1821.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.