The role of FTO variants in the susceptibility of polycystic ovary syndrome and in vitro fertilization outcomes in Chinese women

Abstract

We investigated the association between single nucleotide polymorphisms (SNPs) in the fat mass and obesity associated (FTO) gene (rs9926289 A/G, rs79206939 A/G, rs9930506 A/G, rs8050136 A/C, and rs1588413 C/T) and polycystic ovary syndrome (PCOS), as well as outcomes of in vitro fertilization (IVF). A case-control study consisting of 147 PCOS patients and 120 healthy controls was conducted. FTO SNPs were genotyped by PCR to determine allelic frequencies, and IVF outcomes were analyzed. The results showed that FTO rs8050136 (p = .025) and rs1588413 (p = .042) were significantly associated with PCOS susceptibility, and women with risk alleles were often found to be obese (p < .05). For SNP rs8050136, women with AA + AC genotypes had higher body mass indexes (BMIs), oral glucose tolerance test/2 h (OGTT) levels and implantation rates but lower follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) day progesterone levels and ovulation numbers (all p < .05) than those with the CC genotype. For SNP rs1588413, women carrying risk alleles exhibited higher BMIs, implantation rate, and levels of luteinizing hormone (LH), estradiol, and OGTT/2 h (all p < .05) compared with those with non-risk genotypes. Therefore, these findings suggest that rs8050136 and rs1588413 are associated with PCOS susceptibility, and that women with risk alleles have less ovulation numbers but higher implantation rates than those with other genotypes.

Chinese abstract

FTO变异体在中国多囊卵巢综合征患者易感性和体外受精结局中的作用

摘要

本研究探讨了肥胖基因（FTO）（rs9926289 A/G, rs79206939 A/G, rs9930506 A/G, rs8050136 A/C和rs1588413 C/T）与多囊卵巢综合征（PCOS）的单核苷酸多态性（SNPs）以及体外受精（IVF）结局的关系。入组147名PCOS患者和120名体健者进行病例对照研究。通过PCR法检测等位基因频率以确定FTO SNPs的基因分型, 并对IVF结局进行分析。结果显示, FTO基因 rs8050136和rs1588413与PCOS易感性显著相关（分别为p = 0.025和p = 0.042）, 携带风险等位基因的女性多发生肥胖（p < 0.05）。对于SNP rs8050136, 与CC基因型女性相比, AA + AC基因型女性的体重指数（BMIs）、口服葡萄糖耐量试验/2小时（OGTT）血糖水平和胚胎着床率较高, 但卵泡刺激素（FSH）和人绒毛膜促性腺激素（hCG）日黄体酮水平和排卵数均降低（p < 0.05）。对于SNP rs1588413, 与非风险基因型携带者相比, 携带风险等位基因的女性的BMIs、胚胎着床率、黄体生成素（LH）水平、雌二醇水平和OGTT/2 h水平均升高（p <0.05）。以上研究结果表明, 基因rs8050136和rs1588413与PCOS易感性相关, 且与其他基因型相比, 携带风险等位基因女性的排卵次数减少而胚胎着床率升高。

关键词: 多囊卵巢综合征, FTO, 多态性, IVF, BMI

Keywords:

• Polycystic ovary syndrome
• FTO
• polymorphism
• IVF
• BMI

Acknowledgments

Dr. Kai Li proofread this article. We thank Dr. Sarah Williams for editing the English text of a draft of this manuscript.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by grants from the National Science Foundation of China [31371277] and the Natural Science Foundation of Hunan Province [2016JJ6126] and [2017JJ2380].