Abstract
Leukotrienes are potent inflammatory 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-five polymorphic SNPs were ranked for predicted functional effect using FastSNP. Finally, 14 functional SNPs along with 10 SNPs identified 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 significant 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) (P=0.003), with greater risk being associated with the top quartile as compared to the bottom quartile after adjusting for potential confounders (OR 8.94, 95% CI 2.56–31.95; P=0.001). Four SNPs in the LTA4H gene showed significant association with LTB4 levels (P<0.05) of which rs1978331 (P=0.035) remained significant after correction for multiple testing. LTB4 showed strong correlation with lipids (r=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.
Highlights
Both genetics and environmental factors combined with unhealthy lifestyle play an important role in the development of coronary artery disease (CAD) [1]
Leukotrienes are potent proinflammatory mediators belonging to the 5-lipoxygenase pathway, involved in Arachidonic acid metabolism
ALOX5, ALOX5AP, LTA4 Hydrolase (LTA4H), and LTC4 Synthase (LTC4S) genes and their metabolic products have been investigated with regard to their role in the pathogenesis of cardiovascular disease [28]
Summary
Both genetics and environmental factors combined with unhealthy lifestyle play an important role in the development of coronary artery disease (CAD) [1]. Hypercholesterolemia and inflammation are two key players in CAD [2]. 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]. These Leukotrienes modulate immune response by triggering the synthesis and release of cytokines and interacting with their cognate receptors [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
