Cargando…

Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation

BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolon...

Descripción completa

Detalles Bibliográficos
Autores principales: Gondalia, Rahul, Avery, Christy L., Napier, Melanie D., Méndez-Giráldez, Raúl, Stewart, James D., Sitlani, Colleen M., Li, Yun, Wilhelmsen, Kirk C., Duan, Qing, Roach, Jeffrey, North, Kari E., Reiner, Alexander P., Zhang, Zhu-Ming, Tinker, Lesley F., Yanosky, Jeff D., Liao, Duanping, Whitsel, Eric A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Environmental Health Perspectives 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714283/
https://www.ncbi.nlm.nih.gov/pubmed/28749367
http://dx.doi.org/10.1289/EHP347
_version_ 1783283557346574336
author Gondalia, Rahul
Avery, Christy L.
Napier, Melanie D.
Méndez-Giráldez, Raúl
Stewart, James D.
Sitlani, Colleen M.
Li, Yun
Wilhelmsen, Kirk C.
Duan, Qing
Roach, Jeffrey
North, Kari E.
Reiner, Alexander P.
Zhang, Zhu-Ming
Tinker, Lesley F.
Yanosky, Jeff D.
Liao, Duanping
Whitsel, Eric A.
author_facet Gondalia, Rahul
Avery, Christy L.
Napier, Melanie D.
Méndez-Giráldez, Raúl
Stewart, James D.
Sitlani, Colleen M.
Li, Yun
Wilhelmsen, Kirk C.
Duan, Qing
Roach, Jeffrey
North, Kari E.
Reiner, Alexander P.
Zhang, Zhu-Ming
Tinker, Lesley F.
Yanosky, Jeff D.
Liao, Duanping
Whitsel, Eric A.
author_sort Gondalia, Rahul
collection PubMed
description BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). METHODS: Using repeated electrocardiograms (1986–2004), longitudinal data on [Formula: see text] in diameter ([Formula: see text]), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately [Formula: see text] [Formula: see text] interactions among nine Women’s Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations ([Formula: see text]), then combined subpopulation-specific results in a fixed-effects, inverse variance-weighted meta-analysis. RESULTS: A common variant (rs1619661; coded allele: T) significantly modified the [Formula: see text] association ([Formula: see text]). At [Formula: see text] concentrations [Formula: see text] percentile, QT increased 7 ms across the CC and TT genotypes: 397 (95% confidence interval: 396, 399) to 404 (403, 404) ms. However, QT changed minimally across rs1619661 genotypes at lower [Formula: see text] concentrations. The rs1619661 variant is on chromosome 10, 132 kilobase (kb) downstream from CXCL12, which encodes a chemokine, stromal cell-derived factor 1, that is expressed in cardiomyocytes and decreases calcium influx across the L-type [Formula: see text] channel. CONCLUSIONS: The findings suggest that biologically plausible genetic factors may alter susceptibility to [Formula: see text]-associated QT prolongation in populations protected by the U.S. Environmental Protection Agency’s National Ambient Air Quality Standards. Independent replication and functional characterization are necessary to validate our findings. https://doi.org/10.1289/EHP347
format Online
Article
Text
id pubmed-5714283
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Environmental Health Perspectives
record_format MEDLINE/PubMed
spelling pubmed-57142832017-12-05 Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation Gondalia, Rahul Avery, Christy L. Napier, Melanie D. Méndez-Giráldez, Raúl Stewart, James D. Sitlani, Colleen M. Li, Yun Wilhelmsen, Kirk C. Duan, Qing Roach, Jeffrey North, Kari E. Reiner, Alexander P. Zhang, Zhu-Ming Tinker, Lesley F. Yanosky, Jeff D. Liao, Duanping Whitsel, Eric A. Environ Health Perspect Research BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). METHODS: Using repeated electrocardiograms (1986–2004), longitudinal data on [Formula: see text] in diameter ([Formula: see text]), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately [Formula: see text] [Formula: see text] interactions among nine Women’s Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations ([Formula: see text]), then combined subpopulation-specific results in a fixed-effects, inverse variance-weighted meta-analysis. RESULTS: A common variant (rs1619661; coded allele: T) significantly modified the [Formula: see text] association ([Formula: see text]). At [Formula: see text] concentrations [Formula: see text] percentile, QT increased 7 ms across the CC and TT genotypes: 397 (95% confidence interval: 396, 399) to 404 (403, 404) ms. However, QT changed minimally across rs1619661 genotypes at lower [Formula: see text] concentrations. The rs1619661 variant is on chromosome 10, 132 kilobase (kb) downstream from CXCL12, which encodes a chemokine, stromal cell-derived factor 1, that is expressed in cardiomyocytes and decreases calcium influx across the L-type [Formula: see text] channel. CONCLUSIONS: The findings suggest that biologically plausible genetic factors may alter susceptibility to [Formula: see text]-associated QT prolongation in populations protected by the U.S. Environmental Protection Agency’s National Ambient Air Quality Standards. Independent replication and functional characterization are necessary to validate our findings. https://doi.org/10.1289/EHP347 Environmental Health Perspectives 2017-06-08 /pmc/articles/PMC5714283/ /pubmed/28749367 http://dx.doi.org/10.1289/EHP347 Text en EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
spellingShingle Research
Gondalia, Rahul
Avery, Christy L.
Napier, Melanie D.
Méndez-Giráldez, Raúl
Stewart, James D.
Sitlani, Colleen M.
Li, Yun
Wilhelmsen, Kirk C.
Duan, Qing
Roach, Jeffrey
North, Kari E.
Reiner, Alexander P.
Zhang, Zhu-Ming
Tinker, Lesley F.
Yanosky, Jeff D.
Liao, Duanping
Whitsel, Eric A.
Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation
title Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation
title_full Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation
title_fullStr Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation
title_full_unstemmed Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation
title_short Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation
title_sort genome-wide association study of susceptibility to particulate matter–associated qt prolongation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714283/
https://www.ncbi.nlm.nih.gov/pubmed/28749367
http://dx.doi.org/10.1289/EHP347
work_keys_str_mv AT gondaliarahul genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT averychristyl genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT napiermelanied genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT mendezgiraldezraul genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT stewartjamesd genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT sitlanicolleenm genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT liyun genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT wilhelmsenkirkc genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT duanqing genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT roachjeffrey genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT northkarie genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT reineralexanderp genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT zhangzhuming genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT tinkerlesleyf genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT yanoskyjeffd genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT liaoduanping genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation
AT whitselerica genomewideassociationstudyofsusceptibilitytoparticulatematterassociatedqtprolongation