Hindawi Publishing Corporation ISRN Vascular Medicine Volume 2013, Article ID 985743, 10 pages http://dx.doi.org/10.1155/2013/985743 Research Article Association of Leukotriene Gene Variants and Plasma LTB4 Levels with Coronary Artery Disease in Asian Indians Jiny Nair, 1 Jayashree Shanker, 1 Prathima Arvind, 1 Srikarthika Jambunathan, 1 and Vijay V. Kakkar 2,3 1 Mary and Garry Weston Functional Genomics Unit, Trombosis Research Institute, Narayana Hrudayalaya 258/A, Bommasandra Industrial Area, Anekal Taluk, Bangalore, Karnataka 560099, India 2 Trombosis Research Institute, Bangalore 560099, India 3 Trombosis Research Institute, London, SW3 6LR, UK Correspondence should be addressed to Jayashree Shanker; jayashreeshanker@triindia.org.in Received 24 April 2013; Accepted 14 May 2013 Academic Editors: D. Guidolin, A. Mugge, B. Tesfamariam, and C.-C. Wu Copyright © 2013 Jiny Nair et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Leukotrienes are potent infammatory and lipid mediators that participate in atherosclerosis. We analyzed the association of Leukotriene gene (ALOX5, ALOX5AP, LTA4H, and LTC4S) polymorphisms and plasma Leukotriene B4 (LTB4) levels with coronary artery disease (CAD) in a representative cohort of Asian Indians. In all, 136 functional single nucleotide polymorphisms (SNPs) were selected using in silico tools. Forty-fve polymorphic SNPs were ranked for predicted functional efect using FastSNP. Finally, 14 functional SNPs along with 10 SNPs identifed from the literature were genotyped in 340 CAD patients and 340 controls. Plasma LTB4 levels were measured in 150 cases and 150 controls. None of the 24 SNPs showed signifcant association with CAD. Plasma LTB4 levels were higher in cases than in controls (76.42 ± 4.46 pg/mL versus 60.89 ± 2.61 pg/mL) ( = 0.003), with greater risk being associated with the top quartile as compared to the bottom quartile afer adjusting for potential confounders (OR 8.94, 95% CI 2.56–31.95;  = 0.001). Four SNPs in the LTA4H gene showed signifcant association with LTB4 levels ( < 0.05) of which rs1978331 ( = 0.035) remained signifcant afer correction for multiple testing. LTB4 showed strong correlation with lipids ( = 0.24–34) only in cases. Our pilot study suggests that the association between Leukotrienes gene polymorphisms and CAD risk may be modulated through plasma LTB4 levels. 1. Introduction Both genetics and environmental factors combined with unhealthy lifestyle play an important role in the develop- ment of coronary artery disease (CAD) [1]. Hypercholes- terolemia and infammation are two key players in CAD [2]. Leukotrienes act as mediators in the lipid and infammatory pathway and are synthesized from Arachidonic acid through a cascade process in immune-competent cells. During this process, 5-lipoxygenase (ALOX5) in association with 5- LO activating protein (ALOX5AP), metabolizes Arachidonic acid to Leukotriene A4 (LTA4). LTA4 is unstable and is further converted to Leukotriene B4 (LTB4) and Cysteinyl Leukotrienes (LTC4, LTD4, and LTE4) by LTA4 Hydrolase (LTA4H) and LTC4 Synthase (LTC4S) enzymes, respectively [3]. Tese Leukotrienes then modulate immune response by triggering the synthesis and release of cytokines and interacting with their cognate receptors [4]. Leukotrienes are known to play a signifcant role in CAD development, based on biochemical, genetic, and phar- macological studies [5–7]. Immunohistochemical studies demonstrate abundant expression of Leukotrienes on the arterial walls [8, 9], which correlate with symptoms of plaque instability [10]. Population studies have also explored the association of Leukotriene gene polymorphisms with cardio- vascular disease. Te deCODE Genetics group identifed two distinct haplotypes, Hap A and Hap B in the ALOX5AP gene through linkage study, that were associated with elevated risk of myocardial infarction (MI) and stroke in two independent cohorts. Further, functional studies provided evidence that these variants induce excess production of LTB4 [11, 12]. Te