rs17222814

This study evaluated the genetic contribution of 15 leukotriene pathway genes to coronary artery disease (CAD) risk in 4,512 subjects. Using a two-stage association analysis in Caucasians, LTA4H rs2540477 increased CAD risk (OR=1.2, 95% CI 1.1-1.5; p=0.003), while PLA2G4A rs12746200 decreased CAD risk (OR=0.7, 95% CI 0.6-0.9; p=0.0007) and reduced MACE over 3 years (HR=0.7, 95% CI 0.5-0.9; p=0.01). Functional studies showed monocytes from carriers of LTA4H variants HapK and rs2540477 produced 50% and 33% higher leukotriene B4 levels, respectively, consistent with atherogenic mechanisms.

Genetic association study of leukotriene biosynthesis pathway genes (ALOX5AP, LTA4H, ALOX5) with early-onset coronary artery disease in 1,061 CATHGEN case-control subjects and 1,101 GENECARD families. The four-SNP haplotype (HapA) in ALOX5AP was associated with EOCAD (P=0.02) and the ten-SNP haplotype (HapK) in LTA4H with EOCAD (P=0.04) in CATHGEN. SNPs in ALOX5 showed association with CVD (P<0.05), with specific variants including rs10900215 (P=0.05), rs3740107 (P=0.04), and rs1487562 (P=0.03) associated with EOCAD. Expression analysis revealed pathway interactions among ALOX5, ALOX5AP, and LTA4H in atherosclerotic aorta tissue.

Case-control and replication study examining ALOX5 and ALOX5AP polymorphisms and coronary artery disease (CAD) risk in 1,552 CAD cases and 1,583 controls from the ADVANCE study and ARIC cohort. A nominally significant association was detected between rs12762303 (ALOX5 promoter) and CAD in white/European subjects (OR=1.32 per minor allele; P=0.002), but this association could not be reproduced in the ARIC replication study (HR=1.08; P=0.2). No significant associations were observed for other SNPs tested in either gene, leading to the conclusion that common allelic variation in ALOX5 and ALOX5AP does not provide strong evidence for CAD susceptibility.