Research question

Can single-nucleotide polymorphisms (SNP) of genes related to progesterone synthesis predict the risk of premature serum progesterone elevation in women undergoing gonadotrophin-releasing hormone agonist protocols for ovarian stimulation?

Design

A total of 765 women were divided into high progesterone and normal progesterone groups according to progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration, with the 75th percentile as the threshold between the group. Associations were analysed of genetic information from whole exome sequencing and the clinical characteristics of the two groups to identify the relationship between SNP, haplotypes and serum progesterone elevation.

Results

Among 40 common SNP of eight genes (FSHR, LHCGR, ESR1, ESR2, PGR, HSD3B1, CYP11A1 and CYP17A1), no statistical significance between the high and normal progesterone groups was identified in the distribution of genotypes and allele frequencies after multiple test correction to adjust the false discovery rate (P_FDR > 0.05). When compared with the most common haplotypes of each gene, haplotype GAAG in CYP17A1 was associated with a 1.44-fold increased risk of progesterone elevation (95% confidence interval [CI] 1.22–1.69, P_FDR < 0.001), while haplotypes of the following genes showed a decreased risk of progesterone elevation: haplotype CC in FSHR and LHCGR (0.66-fold, P_FDR = 0.020, and 0.64-fold, P_FDR < 0.001, respectively), CA in ESR1 (0.90-fold, P_FDR < 0.001), TCTGG in ESR2 (0.92-fold, P_FDR = 0.007) and GAACC in HSD3B1 (0.42-fold, P_FDR < 0.001).

Conclusions

Polymorphism in genes involved in enzymes or hormone receptors in the progesterone synthesis pathway may have a role in modifying risk of serum progesterone elevation.

中文翻译：

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在接受长期 GnRH 激动剂方案的女性中，与孕酮升高相关的基因多态性的作用。

研究问题

与孕酮合成相关基因的单核苷酸多态性 (SNP) 能否预测接受促性腺激素释放激素激动剂方案进行卵巢刺激的女性血清孕酮过早升高的风险？

设计

根据人绒毛膜促性腺激素（HCG）给药当天的孕酮浓度，将765名女性分为高孕酮组和正常孕酮组，以第75个百分位作为组间阈值。对来自全外显子组测序的遗传信息和两组的临床特征进行关联分析，以确定 SNP、单倍型和血清孕酮升高之间的关系。

结果

在8个基因（FSHR、LHCGR、ESR1、ESR2、PGR、HSD3B1、CYP11A1和CYP17A1）的40个常见SNP中，经多重检验校正后，高孕酮组与正常孕酮组的基因型分布和等位基因频率无统计学意义。调整错误发现率（P _FDR > 0.05）。当与每个基因的最常见单倍型相比，在单倍型GAAG CYP17A1用1.44倍孕酮高程的风险增加（95％置信区间[CI] 1.22-1.69，相关联的P _FDR <0.001），虽然以下的单倍型基因显示孕酮升高的风险降低：FSHR 中的单倍型 CC和LHCGR（分别为 0.66 倍，P _FDR  = 0.020 和 0.64 倍，P _FDR < 0.001），ESR1 中的CA （0.90 倍，P _FDR < 0.001），ESR2 中的TCTGG （0.92 倍，P _FDR  = 0.007） ) 和 HSD3B1 中的GAACC（0.42 倍，P _FDR < 0.001）。

结论

参与孕酮合成途径中的酶或激素受体的基因的多态性可能在改变血清孕酮升高的风险中起作用。