Patients with polycystic ovary syndrome (PCOS) are suggested to have an aberrant regulation of ovarian Anti-Müllerian Hormone (AMH) expression. Currently, some transcription factors have been demonstrated to play a role in the ovarian regulation of AMH promoter activity. However, still little is known about AMH gene regulation, particularly in women with PCOS. Hence, the aim of this study was to investigate the association of SNPs in the AMH promoter on serum AMH levels in a cohort of PCOS patients.

A candidate gene study was conducted. All two-allelic SNPs located around the AMH promoter (Chr19:2,245,353 – 2,250,827bp) with MAF >1% and imputation quality r² threshold >75% were included. We included Caucasian PCOS women, using the Rotterdam criteria. AMH levels were measured with the picoAMH assay (Ansh Labs®, Houston, Texas, USA). The association between SNPs and AMH was assessed by linear regression and an allele carrier model analysis. All models were adjusted for age, BMI and total follicle count (TFC). AMH levels were natural log transformed to obtain a normal distribution. A p-value below 8.51e-03 was considered as statistically significant, based on Matrix Spectral Decomposition with an effective number of independent variables (VeffLi) of 6. All analyses were performed using R studio.

We assessed 11 SNPs in 700 Caucasian PCOS women. AMH promoter polymorphism rs10406324 (-220 A/G) was associated with serum levels of AMH in the linear regression analysis (β = 0.52, p=6.08e-07) as well as in the dominant carrier model (AA: 9.85 ng/ml ± 0.27 (n=645) vs AG/GG: 7.60ng/ml ± 0.84  (n=54/n=1), p=6.48e-05, F = 16.2). The association of TFC and this SNP showed an inverse trend (β=-8.00, p=3.75e-03), however this result was not significant in the carrier model (AA: 42.2 ± 0.88 (n=645) vs AG/GG: 43.6 ± 2.41 (n=54/n=1), p=0.60, F = 0.281).

The AMH promoter polymorphism rs10406324 is associated with serum AMH levels in Caucasian PCOS women. Functional analyses are necessary to further elucidate the mechanisms by which this SNP affects the AMH promoter activity.