After stratifying the population into two groups by the ESRα promoter methylation level, we found that the risk of T2DM in participants with lower methylation (≤4.07%) were more susceptible to HDL-C (P for interaction = 0.030), as manifested by a decreased of 22% in the risk of T2DM with the increment of each unit SD in HDL-C concentration (Table 5). The gene discussed is ESR1; the disease is type 2 diabetes mellitus.