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PharmGKB Submission Update

PharmGKB Submission Update: VII. PAT Submissions of Genetic Variation in KCND3 to the PharmGKB Network

Vanderbilt University Medical Center, Nashville, Tennessee

Category: genotype

Project: Pharmacogenetics of Arrhythmia Therapy

Table 1 provides the HUGO Gene Nomenclature Committee (HGNC) symbol, PharmGKB submission URLs, submission dates, and release dates. Table 2 provides the HGNC symbol, HGNC names, synonyms, GenBank accession number, and locus ID.

Gene Ontology Terms:

• GO:0005249 voltage-gated potassium channel activity
  
• GO:0005250 A-type (transient-outward) potassium channel activity
  
• GO:0005515 protein binding
  
• GO:0006812 cation transport
  
• GO:0006813 potassium ion transport
  
• GO:0008076 voltage-gated potassium channel complex
  
• GO:0016020 membrane
  
• GO:0016021 integral to membrane
  

Pharmacogenetic Significance: Thorough sequencing of the entire coding region of KCND3 in Caucasian, Asian, and African American individuals yielded no non-synonymous variants and only six synonymous variants.

Pharmacological Significance: I_TO is a key component of cardiac repolarization, a process that is manifest on the surface ECG as the QT interval. The most common cause for drug withdrawal or relabeling in the United States in the last decade is that of drug-induced-variable QT interval prolongation and subsequent development of the potentially lethal ventricular arrhythmia torsade de pointes. Given the role of KCND3 in repolarization, it becomes a candidate gene in mediating this problem.

Potential Drug Interactions: No clinically relevant drug interactions with this channel have been described, with the possible exception of a potential benefit of I_TO block by quinidine (a drug that blocks many ion channels) in a rare congenital arrhythmia syndrome (the Brugada syndrome).

Functional Characteristics: KCND3 encodes the subunit whose expression results in the homotetramer that generates I_TO.

Summary of Data Submitted:

Size of sample set assayed: 190 (380 chromosomes)

Number of gene regions assayed: 7 exons

Total bases assayed: 3219

Coding bases: 1908

Number of variant sites: 6

Polymerase chain reaction primers reported: 24

Footnotes

Supported by National Institutes of Health Grant HL65962 First published on December 30, 2005

Article, publication date, and citation information can be found at http://pharmrev.aspetjournals.org.

doi:10.1124/pr.58.2.1.

¹ Current affiliation: Laval University, Department of Pharmacology, Quebec City, QC, Canada.

This Article Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Simard, C. Articles by Roden, D. Search for Related Content PubMed Articles by Simard, C. Articles by Roden, D.