**2. Candidate gene approach**

#### **2.1 Interleukin-1**

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 Indian population [9].

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

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*Genetic Biomarkers in Periodontal Disease Diagnosis DOI: http://dx.doi.org/10.5772/intechopen.88058*

in Asian populations.

IL-6 and chronic periodontitis [13].

**2.2 Interleukin-6**

**2.3 Interleukin-10**

**2.4 TNF-α**

**2.5 TGF-β**

**2.6 IFN-γ**

authors did not show any association.

(+3954) C > T, could be a significant contribution to the risk of developing periodontitis [10]. Similarly, Yin et al. in their meta-analysis has found an association between IL-1α rs17561 and IL-1β rs 1143634 polymorphisms and periodontitis [11]. IL-1 gene cluster single nucleotide polymorphisms cannot be considered a significant risk factor for all populations. They seem to contribute to risk of periodontitis

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

It is an anti-inflammatory cytokine expressed by T helper cells. It is encoded on gene at 1q31-q32. The major regions of interleukin-10 single nucleotide polymorphisms studied were −1082, −819, and −592. However, conflicting results have been obtained. Berglundh et al. found positive associations between IL-10 SNP and periodontitis in Swedish and Brazilian population [14]. Scarel-Caminaga et al. did

It is a proinflammatory cytokine produced by macrophages. Gene localized at 6p21.3. A meta-analysis by Nikolopoulos et al., which based on 17 studies showed that there was no association of the TNF-α promoter −308G/A polymorphism with periodontitis while another meta-analysis by Song et al. which also included 17 studies found that TNF-α −308 A allele was associated with periodontitis in Brazilian, Asian, and Turkish populations [13]. Ding et al. in their meta-analysis based on 15 studies found an association between TNF-α SNP and periodontitis in Asian and Caucasian population [16]. Thus, the role of TNF-α SNP in the etiopatho-

It is a multifunctional cytokine that plays an important role in cellular differentiation, apoptosis and angiogenesis. It exists in three isoforms TGF-β1, β2, and β3. Cui et al. in their meta-analysis found significant association between TGF-β SNP and periodontitis in Asian population. However, few other studies by different

Produced by natural killer cells. The gene is located on chromosome 12q24. Heidari et al. found an association between IFN-γ SNP in Iranian population, while

not find any significant association in the Caucasian population [15].

genesis of periodontitis has to be explored with further studies.

Holla et al. did not find any significant association [17].

(+3954) C > T, could be a significant contribution to the risk of developing periodontitis [10]. Similarly, Yin et al. in their meta-analysis has found an association between IL-1α rs17561 and IL-1β rs 1143634 polymorphisms and periodontitis [11]. IL-1 gene cluster single nucleotide polymorphisms cannot be considered a significant risk factor for all populations. They seem to contribute to risk of periodontitis in Asian populations.
