학술논문
Novel Genetic Risk and Metabolic Signatures of Insulin Signaling and Androgenesis in the Anovulation of Polycystic Ovary Syndrome
Document Type
article
Author
Xiaoke Wu; Chi Chiu Wang; Yijuan Cao; Jian Li; Zhiqiang Li; Hongli Ma; Jingshu Gao; Hui Chang; Duojia Zhang; Jing Cong; Yu Wang; Qi Wu; Xiaoxiao Han; Pui Wah Jacqueline Chung; Yiran Li; Xu Zheng; Lingxi Chen; Lin Zeng; Astrid Borchert; Hartmut Kuhn; Zi-Jiang Chen; Ernest Hung Yu Ng; Elisabet Stener-Victorin; Heping Zhang; Richard S. Legro; Ben Willem J. Mol; Yongyong Shi
Source
Engineering, Vol 23, Iss , Pp 103-111 (2023)
Subject
Language
English
ISSN
2095-8099
Abstract
Ovulation induction is a first-line medical treatment for infertility in polycystic ovary syndrome (PCOS). Poor ovulation responses are assumed to be due to insulin resistance and hyperandrogenism. In a prospective cohort (PCOSAct) of 1000 infertile patients with PCOS, whole-exome plus targeted single-nucleotide polymorphism (SNP) sequencing and comprehensive metabolomic profiling were conducted. Significant genome-wide common variants and rare mutations associated with anovulation were identified, and a prediction model was built using machine learning. Common variants in zinc-finger protein 438 gene (ZNF438) indexed by rs2994652 (p = 2.47 × 10–8) and a rare functional mutation in REC114 (rs182542888, p = 5.79 × 10–6) were significantly associated with failure of ovulation induction. Women carrying the A allele of rs2994652 and REC114 p.Val101Leu (rs182542888) had lower ovulation (odds ratio (OR) = 1.96, 95% confidence interval (95%CI) = 1.55–2.49; OR = 11.52, 95%CI = 3.08–43.05, respectively) and prolonged time to ovulation (mean = 56.7 versus (vs) 49.0 days, p