In this PCOS case-control study in a Chinese Han population, we found the following genotypes were associated with a lower risk of developing PCOS: GA genotype of rs9340799 in ESR1, TA genotype of rs709154 in PPARG, and CA genotype of rs2272046 in HMGA. Conversely, the GA genotype of rs1999805 in ESR1, and the TT genotype of rs1801133 in MTHFR were significantly associated with increased risk of PCOS. This evidence concerns the gene ESR1 and polycystic ovary syndrome.