Polymorphisms of anti-Müllerian hormone signaling pathway in healthy Singapore women: population differences, endocrine effects and reproductive outcomes

Abstract

In order to study the association of genetic polymorphisms of anti-Müllerian hormone (AMH) signaling pathway with endocrine changes and pregnancy outcomes, a total of 213 women of reproductive ages were recruited according to our inclusion and exclusion criteria between November 2011 and September 2014 in Singapore. Genotyping studies were performed using a minor groove binder primer/probe Taqman assay. The allele frequencies of the AMH Ile⁴⁹Ser and AMHR2 −482A > G polymorphisms were analyzed in relation to female reproductive hormone levels, ovarian parameters, menstrual cycle lengths and pregnancy outcomes. AMH Ser allele frequency and AMHR2 G allele frequency of our Singapore population were compared with those of other populations reported in HapMap. The genotype distributions and allele frequencies for the AMH Ile⁴⁹Ser and AMHR2 −482A > G polymorphisms were not associated with estradiol (E2) levels, ovarian parameters, menstrual cycle length, or pregnancy outcomes in our cohort. Our findings suggest that genetic variants in the AMH signal transduction pathway have population differences but do not appear to have significant effects on ovarian, endocrine, metabolic parameters and reproductive outcomes.

Chinese abstract

为研究抗苗勒氏管激素(AMH)信号通路基因多态性与内分泌变化和妊娠结局的关系，2011年11月至2014年9月依据纳入和排除标准筛选213名新加坡育龄期女性进入研究。采用TapMan-MGB探针法进行基因型分析，并研究了AMH Ile49 Ser 与 AMHR2 −482A＞G 等位基因频率多态性与女性生殖激素水平、卵巢参数、月经周期时长及妊娠结局的关系。HapMap比较了新加坡人群与其他人群AMH Ser与AMHR2 G的等位基因频率。在我们的研究队列中，基因型分布和 AMH Ile⁴⁹ Ser 、AMHR2 −482A＞G等位基因频率多态性与雌激素(E2)水平、卵巢参数、月经周期时长及妊娠结局并无相关性。研究结果表明：AMH信号转导途径的基因变异具有种群差异，但似乎对卵巢、内分泌、代谢参数及生殖结局并无明显影响。

• AMH
• AMHR2
• endocrine changes and reproduction
• polymorphism
• population genetic variation

Acknowledgements

We thank Prof Y.EL’s laboratory members for the acquisition of data, Prof John Carson Allen from Duke-NUS Graduate Medical School Singapore and Prof Michael Kramer from McGill University Canada for revising the manuscript.

Declaration of interest

The authors declare no conflict of interest. This research is supported by the Singapore National Medical Research Council under its Bedside & Bench Grant funding scheme (NMRC/BnB/0007c/2013).

Supplementary material available online