Premature ovarian failure (POF) is defined as the occurrence of amenorrhea before the age of 40 years. It includes primary amenorrhea characterized by absent menarche and secondary amenorrhea represented cessation of ovarian function before the age of 40 years. POF is a polygenic disease, so we performed a whole genome association study to reveal some important genes associated with POF. In this study, we found several regions which were associated with POF. One of the regions strongly associated with POF was on chromosome 6 and encoded protein L‐isoaspartate (D‐aspartate) O‐methyltransferase (PCMT1). We identified that four polymorphisms in PCMT1 gene encoding a protein repair enzyme were associated with POF. Then three polymorphisms formed a haplotype block and were in perfect linkage disequilibrium (LD) through LD test. Haplotype1 had significantly higher frequency in the POF group, while haplotype 2 had significantly higher frequency in the matched control group. Therefore we suggest that ht1 was significantly associated with susceptibility to POF occurance. In contrast, ht2 was significantly associated with resistance to it.