학술논문
Developmental changes in cardiac expression of KCNQ1 and SCN5A spliceoforms: Implications for sudden unexpected infant death.
Document Type
Academic Journal
Author
Williams AF; Vanderbilt University School of Medicine, Nashville, Tennessee.; Bryan AF; Vanderbilt University School of Medicine, Nashville, Tennessee.; Tomasek K; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.; Fulmer CA; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.; Gregory K; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.; Bozeman C; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.; Li F; Forensic Medical Management Services, Nashville, Tennessee.; Absi TS; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.; Su YR; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.; Kannankeril PJ; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: prince.kannankeril@vumc.org.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 101200317 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1556-3871 (Electronic) Linking ISSN: 15475271 NLM ISO Abbreviation: Heart Rhythm Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Sudden unexpected infant death (SUID) occurs unpredictably and remains unexplained after scene investigation and autopsy. Approximately 1 in 7 cases of SUID can be related to a cardiac cause, and developmental regulation of cardiac ion channel genes may contribute to SUID.
Objective: The goal of this study was to investigate the developmental changes in the spliceoforms of SCN5A and KCNQ1, 2 genes implicated in SUID.
Methods: Using reverse transcription quantitative real-time polymerase chain reaction, we quantified expression of SCN5A (adult and fetal) and KCNQ1 (KCNQ1a and b) spliceoforms in 153 human cardiac tissue samples from decedents that succumbed to SUID ("unexplained") and other known causes of death ("explained noncardiac").
Results: There is a stepwise increase in the adult/fetal SCN5A spliceoform ratio from <2 months (4.55 ± 0.36; n = 51) through infancy and into adulthood (17.41 ± 3.33; n = 5). For KCNQ1, there is a decrease in the ratio of KCNQ1b to KCNQ1a between the <2-month (0.37 ± 0.02; n = 46) and the 2- to 4-month (0.28 ± 0.02; n = 52) age groups. When broken down by sex, race, or cause of death, there were no differences in SCN5A or KCNQ1 spliceoform expression, except for a higher ratio of KCNQ1b to KCNQ1a at 5-12 months of age for SUID females (0.40 ± 0.04; n = 9) than for males (0.25 ± 0.03; n = 6) and at <2 months of age for SUID white (0.42 ± 0.03; n = 19) than for black (0.33 ± 0.05; n = 9) infants.
Conclusion: This study documents the developmental changes in SCN5A and KCNQ1 spliceoforms in humans. Our data suggest that spliceoform expression ratios change significantly throughout the first year of life.
(Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
Objective: The goal of this study was to investigate the developmental changes in the spliceoforms of SCN5A and KCNQ1, 2 genes implicated in SUID.
Methods: Using reverse transcription quantitative real-time polymerase chain reaction, we quantified expression of SCN5A (adult and fetal) and KCNQ1 (KCNQ1a and b) spliceoforms in 153 human cardiac tissue samples from decedents that succumbed to SUID ("unexplained") and other known causes of death ("explained noncardiac").
Results: There is a stepwise increase in the adult/fetal SCN5A spliceoform ratio from <2 months (4.55 ± 0.36; n = 51) through infancy and into adulthood (17.41 ± 3.33; n = 5). For KCNQ1, there is a decrease in the ratio of KCNQ1b to KCNQ1a between the <2-month (0.37 ± 0.02; n = 46) and the 2- to 4-month (0.28 ± 0.02; n = 52) age groups. When broken down by sex, race, or cause of death, there were no differences in SCN5A or KCNQ1 spliceoform expression, except for a higher ratio of KCNQ1b to KCNQ1a at 5-12 months of age for SUID females (0.40 ± 0.04; n = 9) than for males (0.25 ± 0.03; n = 6) and at <2 months of age for SUID white (0.42 ± 0.03; n = 19) than for black (0.33 ± 0.05; n = 9) infants.
Conclusion: This study documents the developmental changes in SCN5A and KCNQ1 spliceoforms in humans. Our data suggest that spliceoform expression ratios change significantly throughout the first year of life.
(Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)