ABSTRACT
Objective: To evaluate the association of four single nucleotide polymorphisms (SNPs) in the functional regions, methylation and mRNA expression level of the catechol-Omethyl transferase (COMT) gene with the risk of premature ovarian failure (POF). Methods: According to the POF diagnostic criteria, the participants recruited in this study included 304 patients with POF and 317 healthy women as controls. DNA and RNA were extracted from the peripheral blood. Genotyping of the 4 SNPs was conducted using the SNaPshot method. Methylation and mRNA level was tested by MethylTarget target region methylation sequencing and RT-PCR, respectively. Results: The outcomes showed that the COMT gene rs4680 AA genotype (OR=1.605, 95% CI=1.111-2.319, P=0.011) and A allele (OR=1.277, 95% CI=1.022-1.596, P=0.032) frequencies, methylation level of CpG_8 (t=-2.234, P=0.027) and CpG_10 (t=-2.033, P=0.043) were significantly higher in the POF patients than in the healthy controls. The COMT gene mRNA level was significantly lower in the POF patients than the healthy controls (t=2.071, P=0.041). Conclusion: Our findings indicate that the COMT gene rs4680 A allele, and methylation level of CpG_8 and CpG_10 may be associated with the risk and development of POF by downregulating the COMT gene expression level.