The DRB1*03 and DRB1*15 haplogroups were significantly associated with an increased risk of generalized periodontitis (OR = 19.8, 95% CI = 1.14–346, p = 0.003; OR = 41.2, 95% CI = 1.85–917, p < 0.001) and severe periodontitis (OR = 7.7, 95% CI = 1.68–35.5, p = 0.003; OR = 21.2, 95% CI = 0.97–461, p = 0.005). The gene discussed is HLA-DRB1; the disease is periodontitis.