Polycystic ovary syndrome (PCOS) is diagnosed based on three criteria including a polycystic ovarian morphology (PCOM). Although the etiology of PCOS is not fully understood, a genetic component has been demonstrated. Women with PCOS have elevated serum Anti-Müllerian Hormone (AMH) levels, a hormone known to reflect the ovarian reserve. Little is known about AMH gene regulation, particularly in women with PCOS. Hence, this study aims to investigate the regulation of AMH gene expression in PCOS patients.

A cohort of 700 Caucasian PCOS women were included. All common two-allelic single nucleotide polymorphisms (SNPs), located in the region Chr19:2,245,353–2,250,827bp (hg19), were selected. The association between SNPs and serum AMH levels was analyzed by regression analysis. KK1 cells were used to assess the functional effects of genetic variants.

We assessed 11 SNPs in 700 Caucasian PCOS patients. Polymorphism rs10406324 (−210 A>G) was associated with serum AMH levels in the linear regression model analysis (β = -0.52, p=6.08E-7) and dominant allele carrier model analysis (AA: 9.85±0.27 ng/ml (n=645); AG/GG: 7.60±0.84 ng/ml (n=54/n=1), F=16.2, p=6.48E-5). Stratification by BMI in lean (<25kg/m²) and obese (>30kg/m²) PCOS patients showed that the association was only present in obese PCOS patients (AA: 10.53±0.41 ng/ml (n=295); AG/GG: 8.98±1.63 ng/ml (n=52) P=0.02). Functional analysis showed a significant decrease in basal activity of the AMH promoter construct containing the G variant (P=0.03). In silico analysis suggested a decrease in binding affinity of the transcription factor SF1 for the −210G AMH variant. Although the −210G variant had a lower basal activity, co-transfection of SF1 resulted in a comparable fold increase for both variants.

In conclusion, our results show that the human AMH promoter polymorphism rs10406324 −210G is associated with lower serum AMH levels in Caucasian PCOS women and lead to reduced basal activity of the AMH promoter. However, replication studies and additional functional analysis remain necessary to validate the findings.