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

Citation

Gondalia, Rahul; Avery, Christy L.; Napier, Melanie D.; Mendez-Giraldez, Raul; Stewart, James D.; Sitlani, Colleen M.; Li, Yun; Wilhelmsen, Kirk C.; Duan, Qing; & Roach, Jeffrey, et al. (2017). Genome-Wide Association Study of Susceptibility to Particulate Matter-Associated QT Prolongation. Environmental Health Perspectives, 125(6), 067002. PMCID: PMC5714283

Abstract

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 in diameter (), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately interactions among nine Women's Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (), 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 association (). At concentrations 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 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 channel.
CONCLUSIONS: The findings suggest that biologically plausible genetic factors may alter susceptibility to -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.

URL

http://dx.doi.org/10.1289/ehp347

Reference Type

Journal Article

Year Published

2017

Journal Title

Environmental Health Perspectives

Series Title

R Gondalia et al. Environ Health Perspect 125 (8), 089001. 2017. PMID 28858825.

Author(s)

Gondalia, Rahul
Avery, Christy L.
Napier, Melanie D.
Mendez-Giraldez, Raul
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.

PMCID

PMC5714283

ORCiD

Avery - 0000-0002-1044-8162