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 prolongation in a multi-racial/ethnic, genome-wide association study (GWAS).

METHODS: Using repeated electrocardiograms (1986–2004), longitudinal data on PM

RESULTS: A common variant (rs1619661; coded allele: ) significantly modified the QT-PM association (p=2.11×10). At PM concentrations >90th 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 PM 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 Ca channel.

CONCLUSIONS: The findings suggest that biologically plausible genetic factors may alter susceptibility to PM-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