Deep sequencing identifies novel regulatory variants in the distal promoter region of the dopamine-&bgr;-hydroxylase gene

  title={Deep sequencing identifies novel regulatory variants in the distal promoter region of the dopamine-\&bgr;-hydroxylase gene},
  author={Toyanji Joseph Punchaichira and Suman Prasad and Smita Neelkanth Deshpande and B. K. Thelma},
  journal={Pharmacogenetics and Genomics},
Objective Dopamine-&bgr;-hydroxylase (DBH), an enzyme that converts dopamine into norepinephrine, is a drug target in cardiovascular and neuropsychiatric disorders. We aimed to identify functional variants in this gene by deep sequencing and enzyme phenotyping in an Indian cohort. Materials and methods Targeted resequencing of 12 exons and 10 kb upstream sequences of DBH in healthy volunteers (n=50) was performed using the Ion Personal Genome Machine System. Enzyme quantity and activity in… 

A single nucleotide polymorphism in dopamine beta hydroxylase (rs6271(C>T)) is over-represented in inflammatory bowel disease patients and reduces circulating enzyme

This is the first report of a noradrenergic genetic polymorphism (rs6271; Arg549Cys) associated with IBD, which is associated with significantly lower levels of circulating DβH.

Association of regulatory variants of dopamine β-hydroxylase with cognition and tardive dyskinesia in schizophrenia subjects

With modest genotype–phenotype correlations available for DBH variants, personalized treatment regimens based on DBH activity for ameliorating tardive dyskinesia and cognitive symptoms may be plausible.

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

The role of genetic variants in DβH and its role in health and disease is discussed.

Determination of Dopamine-β-hydroxylase Activity in Human Serum Using UHPLC-PDA Detection

This novel assay employing SPE to separate octopamine and tyramine from the cocktail matrix may have implications for categorising subjects into various risk groups for Schizophrenia, Parkinson’s disease as well as in high throughput screening of inhibitors.

Cardiovascular Pharmacology for the Past 5 Years in India

Cardiovascular pharmacologists in India have been involved in both pre-clinical and clinical validation of the traditional drugs with active governmental support, and realised the need for academia- industry research partnership to carry out meaningful research.



The catecholamine biosynthetic enzyme dopamine β-hydroxylase (DBH): first genome-wide search positions trait-determining variants acting additively in the proximal promoter.

It is concluded that three common SNPs in the DBH promoter act additively to control phenotypic variation in DBH levels, and that two additional novel loci may also contribute to the expression of this catecholamine biosynthetic trait.

Human dopamine beta-hydroxylase (DBH) regulatory polymorphism that influences enzymatic activity, autonomic function, and blood pressure

Investigation of DBH polymorphisms associated with enzymatic activity as well as autonomic and blood pressure (BP)/disease phenotypes in vivo suggests common genetic variation in the DBH promoter region seems to initiate a cascade of biochemical and physiological changes eventuating in alterations of basal BP.

Human dopamine β-hydroxylase promoter variant alters transcription in chromaffin cells, enzyme secretion, and blood pressure.

It is suggested that DBH promoter variant C-2073T is functional in vivo: this promoter variant seems to initiate a cascade of transcriptional and biochemical changes including augmented DBH secretion, eventuating in elevation of basal BP, and hence cardiovascular risk.

Dopamine β-hydroxylase: two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation

The results confirm thatDBH is a major quantitative trait locus for plasma DβH activity, and provide the first direct evidence that DBH also influences CSF D βH levels.

Population genetics of a functional variant of the dopamine beta-hydroxylase gene (DBH).

The observed proportions of DBH*304S homozygotes did not differ significantly from Hardy-Weinberg expectations in any of the populations after Bonferroni correction for multiple comparisons, demonstrating the importance of controlling for population stratification in future studies testing for associations between DBH-304S and clinical phenotypes.

Genotypic and haplotypic associations of the DBH gene with plasma dopamine β-hydroxylase activity in African Americans

The relationship between DBH polymorphisms and pDβH in samples from African-American subjects and the importance of analyzing multiple SNPs across DBH in future association studies examining disease and biochemical phenotypes are examined.

A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus.

It is demonstrated that --1021C-->T is a major genetic marker for plasma-D beta H activity and provide new tools for investigation of the role of both D beta H and the DBH gene in human disease.

Dopamine Beta‐Hydroxylase (DBH) gene and schizophrenia phenotypic variability: A genetic association study

  • Kenji YamamotoJ. Cubells R. Joober
  • Psychology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2003
The results suggest that the DBH gene is not a causative factor in schizophrenia but that it may be a modulator of psychotic symptoms, severity of the disorder and therapeutic response to neuroleptic drugs.

Role of polymorphisms in dopamine synthesis and metabolism genes and association of DBH haplotypes with Parkinson's disease among North Indians

Assessment of contribution of six genes involved in dopamine synthesis and metabolism to PD susceptibility and its role in modulating disease severity reiterates the importance of dopamine pathway in sporadic PD etiology in general and potential therapeutic implications of DBH in particular.

A haplotype at the DBH locus, associated with low plasma dopamine β-hydroxylase activity, also associates with cocaine-induced paranoia

The two DBH polymorphisms studied are associated with plasma DBH levels; those two polymorphisms are in significant linkage disequilibrium in European Americans; and the haplotype associated with low DBH activity is also associated with cocaine-induced paranoia.