Abstract 16041: Interaction of Genetic Variation at the ABO Locus With Short-Term Exposure to Elevated Fine Particulate Matter Air Pollution Results in Differential Associations With Acute Coronary Events

Introduction: Fine particulate matter (PM 2.5 ) air pollution is associated with risk of acute coronary syndrome (ACS) events primarily in patients with coronary artery disease (CAD). ABO gene sequence variants rs687289 and rs514659 (r 2 =1.0 with rs687289) were previously validated by GWAS to predict myocardial infarction (MI) in CAD patients. Hypothesis: Short-term exposure to elevated PM 2.5 is differentially associated with ACS event risk in carriers of ABO rs687289 A allele vs. GG genotype. Methods: Patients who had ≥1 coronary vessel with flow-limiting CAD (≥70% stenosis) and resided on Utah’s Wasatch Front were studied if they were hospitalized at Intermountain Healthcare for an ACS event (acute MI or unstable angina) and donated a DNA sample for genetic testing between October, 1993 and May, 2007. ABO variants rs687289 (primary hypothesis), rs657152 (r 2 =0.86 with rs687289), and rs579459 (r 2 =0.40 with rs687289) were genotyped. A time-stratified case-crossover design was used in which a patient’s PM 2.5 exposure at the time of an ACS event was matched to exposures at non-event times on the same day of the week and in the same month. Odds ratios (OR) for PM 2.5 with adjustment for daily temperature, dew point, and barometric pressure were determined for linear models using a 25 μg/m 3 threshold and in non-threshold models. Results: Patient age averaged 53±7 years, 27% were female, and characteristics were similar across genotypes. Short-term PM 2.5 exposure was associated with ACS events in carriers of the rs687289 A allele, but not in GG genotype (Table). Results also differed by rs657152 A allele carriage (OR=1.23, p=0.008) vs. CC genotype (OR=1.12, p=0.21), but not by rs579459 C allele carriage (OR=1.19, p=0.07) vs. TT genotype (OR=1.15, p=0.06). Conclusion: Short-term exposure to elevated PM 2.5 was associated more strongly with risk of ACS events in ABO risk allele carriers. Additional studies should evaluate interactions of genetic factors with PM 2.5 air pollution.