In a cross-classification interaction, considering polymorphisms and gender, TLR4 896 A/G genotype was associated with periodontitis in men when compared to the A/A wild genotype in females (OR = 2.86, 95%CI: 1.02-8.00; all subjects), and TLR4 1196 C/C wild genotype and RANKL A/A genotype were associated with periodontitis in nonsmoking men when compared to the same genotype in nonsmoking women (OR = 1.85, 95%CI: 1.03-3.28, and OR = 1.96, 95%CI: 1.01-3.78). The gene discussed is TLR4; the disease is periodontitis.