Evaluation of the association of ALOX15 gene polymorphism in patients with periodontitis -a case -control study

Periodontitis is a multifactorial immuno-inflammatory disease that occurs due to complex interaction between pathogenic bacteria and host response. There is a complex network of anti and pro-inflammatory cytokines, prostaglandins, reactive oxygen species and proteolytic enzymes involved in this inflammatory responses. Studies have suggested that periodontal disease pathogenesis is due to the failure of resolutory pathways in the periodontal tissues. The resolution of inflammation, also known as catabasis, is necessary for return to tissue homeostasis and prevention of acute inflammation progression to chronic inflammation. This has led to investigations on the role of specialized proresolving lipid mediators (SPMs) like lipoxins, resolvins, protectins and maresins on periodontalinflammation. SPMs are omega-6 or omega-3 fatty acid-derived metabolites produced by the cyclooxygenase and lipoxygenase pathways, with anti- inflammatory and pro-resolving effects . Immunoresolvents play anti‐ inflammatory and pro‐resolving roles through several mechanisms, such as inhibition of infiltration and migration of polymorphonuclear neutrophils (PMNs), stimulation of the apoptosis of exhausted PMN cells, efferocytosis by macrophages, and counter-regulation of cytokines and chemokines. For this reason, Arachidonate 15-lipoxygenase (ALOX15) has attracted much attention for its role in contributing to active resolution of the inflammatory process.Arachidonate 15-lipoxygenase (ALOX15) is a member of the lipid peroxidizing enzyme family, involved in the biosynthetic pathway of some immunoresolvents like Lipoxins and Resolvins. ALOX15 is expressed in the cells of the hematopoietic, endocrine, immune, and respiratory systems and plays an important role in maintaining body homeostasis. ALOX15 was reported to oxygenate AA and docosahexaenoic acid and synthesize SPM precursor lipids namely 15-HETE and 17-HDHA respectively . Further, 15-HETE is used for Lipoxins synthesis and 17-HDHA is used for the synthesis of Resolvins and Protectins. Hence ALOX 15 is a key enzyme involved in the synthesis of specialized pro-resolving mediators (SPMs) including lipoxins (LXs), resolvins (Rvs), protectins, and maresins that facilitate inflammation resolution. LXA4 decreases production of MMP-3 and increases TIMP production . Lipoxin A4 inhibits the expression of IL-1β, IL-6, and TNF-α meanwhile it improves the expression ofantiinflammatory cytokines like IL-10. In a study it was demonstrated that generation of reactive oxygen species from neutrophils stimulated by Porphyromonas gingivalis was inhibited by LXA4. Serhan et al suggested that lipoxins have a protective role on periodontal inflammation and alveolar bone resorption. Lipoxins have a wide range of actions on myeloid cells and since myeloid cells play an important role in periodontal disease pathogenesis Hence the observations from the above studies emphasize that The 15-LOX enzyme and the associated metabolites are critical players in both the generation and resolution of inflammation. Human 15-LOX is encoded by the ALOX15 gene, which is located on chromosome 17p13.3 and consists of 14 exons separated by 13 introns in the LOX gene cluster. Several studies on single-nucleotide polymorphisms (SNPs) have confirmed the association of ALOX15 SNPs with various inflammatory disorders like allergic rhinitis and ischemic heart disease. However, no research has yet investigated the polymorphisms of ALOX15 gene in periodontitis..It is plausible to hypothesize that the genetic polymorphisms of ALOX 15 gene may predispose or protect the individuals from developing periodontitis. This case-control study aimed to assess and compare the association of rs7217186:C>T of ALOX 15 gene polymorphism in patients with and without periodontitis.