Introduction: The polycystic ovary syndrome (PCOS) is a common and complex disease without a clear pattern of inheritance. There is evidence that PCOS is affected by both genetic and environmental factors, but there is no single and unambiguous explanation for its pathogenesis. Anti-Müllerian-inhibiting hormone (AMH) has an inhibitory effect on FSH-stimulated follicle growth and it has also been shown that serum AMH levels are higher in women with PCOS than in normovulatory women. The elevated AMH levels may reflect abnormalities at the AMH receptor. The current study examined the AMH receptor 2 (AMHR2) −482 A>G polymorphism (rs2002555) in a large cohort of PCOS women. The large number of the participants as well as their ethnic homogeneity enhanced the ability to detect a potential correlation between this polymorphism and the PCOS syndrome.
Methods/design: In 858 Caucasian women with PCOS and 312 healthy controls, hormonal determinations and AMHR2 −482 A>G polymorphism genotyping were performed.
Results: The AMHR2 −482 A>G gene polymorphism (rs2002555) was more common in women with PCOS than in controls (P=0.026). The relationship between AMHR2 −482 A>G and PCOS remained when examining only subjects meeting NIH criteria for PCOS. Homozygous AMHR2 −482 A>G gene polymorphisms (GG) were associated with decreased levels of LH (P=0.003) and LH:FSH ratio (P=0.01) in women with PCOS, as well as with lower prolactin levels (P=0.004). No other associations related to AMHR2 −482 A>G polymorphisms were observed in women with PCOS or controls.
Conclusion: In this study, the role of the AMHR2 −482 A>G gene polymorphism in the pathogenesis of PCOS has been suggested by the association of the variant with PCOS risk. The role of AMHR2 −482 A>G SNP in PCOS might result from the diminished improper AMH signaling implicated in altered ovarian function.
27 Apr - 01 May 2013
European Society of Endocrinology