Role of a KCNH2 polymorphism (R1047 L) in dofetilide-induced

Sun, Zhuoqian; Milos, Patrice M.; Thompson, John F.; Lloyd, David B.; Mank-Seymour, Amy R.; Richmond, Jodi; Cordes, Jason; Zhou, Jun

doi:10.1016/j.yjmcc.2004.09.001

Cited by 60 publications

(40 citation statements)

References 34 publications

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“…Mutations in this gene are hypothesized to cause long QT syndrome type 2 (LQT2) [20]. Results of in vitro assays suggested that polymorphisms in KCNH2 affect the functions of the ion channel and contribute to the higher incidence of Torsades de Pointes in the carriers when challenged with a channel blocker [21]. In vitro experiments and clinical studies indicated that domperidone was associated with QT interval prolongation evidently due to interaction with KCNH2 polypeptide [22][23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Domperidone Treatment for Gastroparesis: Demographic and Pharmacogenetic Characterization of Clinical Efficacy and Side-Effects

et al. 2010

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Genetic characteristics associated with response to domperidone therapy included polymorphisms in the drug transporter gene ABCB1, the potassium channel KCNH2 gene, and α1D--adrenoceptor ADRA1D gene. Age was associated with a beneficial response to domperidone. If verified in a larger population, this information might be used to help determine which patients with gastroparesis might respond to domperidone and avoid treatment in those who might develop side-effects.

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Section: Discussionmentioning

confidence: 99%

Domperidone Treatment for Gastroparesis: Demographic and Pharmacogenetic Characterization of Clinical Efficacy and Side-Effects

et al. 2010

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“…For example, five of the SIDS victims were positive for R1047L-KCNH2, a polymorphism previously identified as an independent risk factor for drug (dofetilide)-induced torsades [Sun et al, 2004;Tester and Ackerman, 2005]. In addition, the African American-specific sodium channel common polymorphism, S1103Y-SCN5A, was overrepresented among a cohort of 133 African American SIDS infants and a mexiletine-sensitive increased late sodium current was elicited by cellular acidosis [Plant et al, 2006].…”

Section: Significance Of Cardiac Channelopathies In Sidsmentioning

confidence: 94%

Sudden Infant Death Syndrome: Review of implicated genetic factors

Weese‐Mayer

Ackerman

Marazita

et al. 2007

American J of Med Genetics Pt A

123

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Genetic studies in Sudden Infant Death Syndrome (SIDS) have been motivated by clinical, epidemiological, and/or neuropathological observations in SIDS victims, with subsequent pursuit of candidate genes in five categories: (1) genes for ion channel proteins based on electrocardiographic evidence of prolonged QT intervals in SIDS victims, (2) gene for serotonin transporter based on decreased serotonergic receptor binding in brainstems of SIDS victims, (3) genes pertinent to the early embryology of the autonomic nervous system (ANS) (and with a link to the 5-HT system) based on reports of ANS dysregulation in SIDS victims, (4) genes for nicotine metabolizing enzymes based on evidence of cigarette smoking as a modifiable risk factor for SIDS, and (5) genes regulating inflammation, energy production, hypoglycemia, and thermal regulation based on reports of postnatal infection, low birth weight, and/or overheating in SIDS victims. Evidence for each of these classes of candidate genes is reviewed in detail. As this review indicates, a number of genetically controlled pathways appear to be involved in at least some cases of SIDS. Given the diversity of results to date, genetic studies support the clinical impression that SIDS is heterogeneous with more than one entity and with more than one possible genetic etiology. Future studies should consider expanded phenotypic features that might help clarify the heterogeneity and improve the predictive value of the identified genetic factors. Such features should be evaluated to the extent possible in both SIDS victims and their family members. With 2,162 infants dying from SIDS in 2003 in the U.S. alone, and improved but still imperfect parent and caretaker compliance with known modifiable risk factors for SIDS, it behooves clinicians, researchers, and parents to combine efforts to reach a common goal. The message of the "Back to Sleep" campaign needs to be re-introduced/re-engineered to reach families and caretakers of all ethnic groups. Clinicians and researchers need to gently inform new SIDS parents about the opportunity to contribute tissue to the NICHD-funded University of Maryland Brain and Tissue Bank. By expanding the network of clinicians, scientists, and families working together, and by combined efforts in a collaborative multi-center study of candidate genes and/or genomics, the discovery of the genetic profile of the infant at risk for SIDS can ultimately be determined.

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“…Stable human embryonic kidney (HEK)-293 cells expressing the hERG channel (Zhou et al, 1998) were licensed from Wisconsin Alumni Research Foundation or generated in-house. Methods for cell culture and whole cell patch-clamp studies on the hERG channel were reported previously (Volberg et al, 2002;Sun et al, 2004;Cordes et al, 2005). EPC-9 (HEKA, Lambrecht/Pfalz, Germany) or MultiClamp 700A (Axon Instruments Inc., Union City, CA) amplifiers were employed to record the current controlled by Pulse ϩ PulseFit 8.40 (HEKA) or pClamp 8.2 (Axon Instruments) software through an interface.…”

Section: Methodsmentioning

confidence: 99%