Determination of Cofilin-2 (rs80358250) and Lactoferrin (rs1126478) Genetic Polymorphism and Change in Their Protein Levels Before and After Non-surgical Periodontal Therapy in Periodontitis Patients With and Without Coronary Heart Disease - An Interventional Study.

Periodontitis is a chronic multifactorial inflammatory disease associated with the accumulation of dental plaque and characterized by progressive destruction of the teeth-supporting apparatus, including the periodontal ligament and alveolar bone. Dental plaque accumulation at the gingival margin initiates an inflammatory response that, in turn, causes microbial alterations and may lead to drastic consequences in the periodontium of susceptible individuals. The pathophysiology of periodontitis is influenced by the relationship between the host immune system and periodontal pathogens. The presence of periodontal pathogens and their metabolic by-products in the oral cavity may get disseminated to the systemic circulation which may pose a risk for various systemic diseases such as cardiovascular disease, oral and colorectal cancer, gastrointestinal diseases, respiratory tract infection, adverse pregnancy outcomes and diabetes.

Although pathogenic bacteria and various other environmental factors are involved in pathogenesis of periodontitis, genetic factors are also known to play a pivotal role in influencing the inflammatory and immune response. Genetic polymorphisms are alterations in the DNA sequence found in general population. Most forms of periodontitis represent a life-long account of interactions between the genome and the environment. The previous literature has stated a strong association of genetic polymorphisms in periodontitis and coronary artery diseases. Identifying these polymorphisms can potentially lead to a better understanding of the mechanisms modulating the expression of inflammatory mediators as well as provides potential therapeutic targets in the prevention of periodontal disease. Two such novel polymorphisms have gained attention recently, namely the Cofilin-2 and Lactoferrin polymorphisms.

Cofilin is one of the most affluent and common actin-binding proteins and plays a role in cell motility, migration, shape, and metabolism. They also play an important role in severing actin filament, nucleating, depolymerizing and bundling activities. Cofilin is the major ADF/cofilin isoform in mammalian neurons influences the dynamics of actin assembly by severing or stabilizing actin filaments. Cofilin-2 is the only isoform present in mature skeletal muscles. It is composed of 5 α helices, 5 β sheets, and 1 C-terminal β short chain, with a molecular weight of 18 kDa. Cofilin-2 is a member of the AC group of proteins that also includes cofilin-1 and destrin, all of which regulate actin-filament dynamics. Recently, Cofilin 2 gained attention as an emerging biomarker for coronary heart diseases. Cofilin-2 has shown to play a role in pathophysiology of coronary heart disease.

Lactoferrin is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears and nasal secretions. Lactoferrin, a multifunctional iron-binding glycoprotein, is involved in coronary heart disease pathophysiology. Recent studies reported that Lactoferrin polymorphism is associated with an increased risk of coronary artery disease in the elderly population.

Studies have been done to identify Lactoferrin genetic polymorphisms, however none of the studies have explored the role of Lactoferrin (rs1126478) and its protein level in subjects with both periodontal disease and coronary heart disease occurring as a continuum. Its expression in periodontitis and coronary heart disease patients is yet to be explored. Genetic polymorphism and protein levels of Cofilin-2 (rs80358250) has been never studied in coronary heart disease and periodontitis. This may further improve our understanding of the influence of this polymorphism on the above mentioned systemic diseases.

NEED FOR THE STUDY While there are studies which have demonstrated the expression of Cofilin-2 and Lactoferrin polymorphisms in various inflammatory conditions, there are no studies to state their expression in the subgingival plaque samples of periodontitis patients with coronary artery disease, specifically before and after non-surgical therapy. Also, the correlation of both these polymorphisms and their levels with periodontal and cardiac parameters has never been investigated so far. It is suggested that these polymorphisms may play a role as putative risk indicators in periodontitis subjects with coronary heart disease which may alter following non-surgical periodontal therapy.