KEY WORDS: AGTR1, ALOX15, cardiac structure, cardiac MRI, gene--environment interactions, left ventricular mass, traffic, air pollution.
Twelve genes were selected from among genotyped MESA candidate genes: ACE, ADRB2, AGT, AGTR1, ALOX15, EDN1, GRK4, PTGS1, PTGS2, TLR4, VEGFA, and VEGFB.
All SNP-traffic proximity interaction models tested demonstrated significant evidence of interactions for two of the 12 genes tested, ALOX15 and AGTR1 [Table 2; see also Supplemental Material, Figure 1 (doi: 10.
Model/Gene tagSNP [rho]-Value Genotype Percent difference in for LVM associated with interaction traffic proximity (95% Cl) Model 1: study site,age, sex, AIMs, height, weight AGTR1 rs389566 0.
We found significant evidence of gene-traffic interactions in MESA, with polymorphisms in AGTR1 and ALOX15, genes important in vascular function and inflammation/oxidative stress, associated with substantial alterations in the association between traffic proximity and LVM.
AGTR1 is a well-known regulator of blood pressure and common target of specific pharmacologic intervention (ARB) in hypertension.
Both ALOX15 and AGTR1 are likely to play important roles in inflammation, one of the primary putative mechanisms for the impact of air pollution on CVD and also an important mechanism involved in the development of left ventricular hypertrophy.
Linkage disequilibrium mapping of AGTR1 and ALOX15 in these analyses suggests that regions near to tagSNPs rs6801836 on AGTR1 and rs2664593 on ALOX15 are responsible for the interactions seen in this study.
Renal function dependent association of AGTR1 polymorphism (A1166C) and electrocardiographic left-ventricular hypertrophy.