**2.2 Interleukin-6**

*Periodontal Disease - Diagnostic and Adjunctive Non-surgical Considerations*

and environmental factors determine the susceptibility to disease.

dependent on the way their bodies responded to the microbes [1]. Genetic factors

A biomarker is a substance that could indicate a biologic state and is an objective measure to evaluate the current and future disease activity. The National Institutes of Health Biomarkers Definitions Working Group in 1998 defined a biomarker as "a substance that is measured objectively and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention." These biomarkers could be determined in various biological media like saliva, serum, and gingival crevicular fluid in health as well as disease. Generally, a combination of biomarkers is used in order to predict disease activity. Genetic susceptibility to multifactorial diseases like periodontitis is usually due to several gene polymorphisms instead of a single, or few, gene mutations. Subtle variations in the genetic code may result in altered expression of the encoded proteins, thereby making individuals with genotypes more susceptible to a given

The genetic link with the etiopathogenesis of periodontitis was started with the initial finding of association of composite genotype (Interleukin-1α and IL-1β) with chronic periodontitis in Caucasian population by Kornman et al. [2]. Following him, lot of studies conducted in different ethnic races linking the association of composite genotype with periodontitis. But the results were contradictory in nature. A variety of single nucleotide polymorphisms of various signaling factors, receptors, connective tissue components, enzymes involved in the host defense against the invading microbes have been reported by several researchers. Use of the genetic risk score could be useful in assessing the susceptibility to periodontitis. However, conflicting results have been reported because of the heterogeneticity of the studies. Different variations in frequency of some alleles in different popula-

Interleukin-1 (IL-1) is a pro-inflammatory cytokine, which is encoded by IL-1 gene cluster at the chromosomal position 2q13–21. It is produced by inflammatory cells such as monocytes, macrophages, and dendritic cells, which play an important role in the regulation of immune and inflammatory responses to infections. It is composed of two molecules, IL-1α and IL-1β. The former regulates intracellular events while the latter acts as an extracellular protein. It plays a major role in the regulation of the inflammatory mechanisms. Studies by Lavu et al., Hao et al. have proposed that IL-1 cluster gene single nucleotide polymorphisms were associated with higher risk for periodontitis [3, 4]. Kornman et al. reported a relationship between IL-1α −889 and IL-1β +3954 and the severity of periodontal disease [2]. Kobayashi et al. demonstrated that Asians had a low carriage rate of IL-1α −889

R-allele compared to the other populations [5]. A meta-analysis by Mao et al., showed that IL-1β +3954 polymorphism increases the risk of periodontal disease [6]. Other authors like Amirisetty et al., Masamatti et al. suggested a strong association of IL-1β −511 and +3954 with chronic periodontitis in Indians [7, 8]. Whereas the study by Kaarthikeyan et al. did not find any significant association between interleukin-1β (+3954) polymorphism with chronic periodontitis in

Karimbux et al. in their systematic review and meta-analysis studied 13 studies and found that IL-1α and IL-1β (IL-1α (−889) C > T, IL-1α (+4845) G > T, IL-1β

**42**

Indian population [9].

disease.

tions have been observed.

**2.1 Interleukin-1**

**2. Candidate gene approach**

Interleukin-6 is produced during inflammation by T cells. It is encoded by the IL-6 gene localized on chromosome 7p21. Interleukin-6 is a potent bone resorbing cytokine. It activates and regulates the osteoclasts. Thus, this plays a major role in the susceptibility and progression of periodontal destruction. Zhang et al. found significant association between IL-6 −1363 G/T and IL-6R +48,892 A/C polymorphisms with periodontitis in Chinese population [12]. In a meta-analysis by Nikolopoulos et al. on cytokine gene polymorphisms such as IL-1α, IL-1β, IL-6, and TNF which included 53 studies, no significant association was detected between IL-6 and chronic periodontitis [13].
