Despite the general overall improvement in periodontal health, periodontitis is still the number one cause of tooth loss in adults. Genetic predisposition to the onset of periodontitis means that some patients can be identified even before disease begins. Genetic heterogeneity associated with disease also extends to treatment responsiveness.

We investigated the association of cytokine gene polymorphism in the Macedonian population with Periodontitis, as a part of the International project Cytokine Polymorphism Component, 13th IHWC.

The Macedonian population consists of 125 healthy unrelated individuals, and 48 patients with Periodontitis. Blood samples were collected after written consent, DNA was isolated from peripheral blood leukocytes by the phenol-chlorophorm extraction method and samples were stored in our Human DNA Bank. Cytokine genotyping was performed by PCR-SSP (Heidelberg kit). The population genetics analysis package (PyPop) was used for analysis of the cytokine data for this report. Comparisons of different alleles, genotypes, haplotypes, and haplotype zygosity for two groups were tested by the two-tailed Fisher Exact Test. Crude odds ratios (OR), as estimates of the relative risk, were calculated with 95% confidence interval (CI).

It was found significant association between the Macedonian patients with Periodontitis and: 1) cytokine alleles IL-4-590 [p=0.020, OR(95%CI)=2.022(1.144-3.575)], and IL-4-33 [p=0.008, OR(95%CI)=2.202(1.248-3.889)]; 2) cytokine genotypes IL-4-590C:T [p=0.002, OR(95%CI)=0.318(0.157-0.642)], IL-4-590C:C [p=0.004, OR(95%CI)=2.853(1.428-5.706)], and IL-4-33T:T [p=0.001, OR(95%CI)=0.136(0.043-0.436)]; 3) cytokine haplotypes IL-4/TCC [p=0.000, OR(95%CI)=0.376(0.228-0.620)], IL-4/TCT [p<0.001, OR(95%CI)=Inf(8.527-Inf)], and IL-4/TTC [p<0.001, OR(95%CI)=26.860(4.342-164.610)]; and cytokine haplotype zygozity TGF-b1CC:CG [p=0.033, OR(95%CI)=Inf(1.667-Inf)], IL-4TCC:TCC [p=0.015, OR(95%CI)=0.406(0.203-0.813)], IL-4TTC:TCC [p=0.001, OR(95%CI)=Inf(3.934-Inf)], IL-4GCC:TCC [p<0.001, OR(95%CI)=Inf(6.365-Inf)], and IL-4GCC:TTC [p=0.027, OR(95%CI)=Inf(1.837-Inf)].

It is concluded that cytokine gene polymorphism in the Macedonian population is associated with Periodontitis.