Identification of common genetic polymorphisms associated with down-regulated gonadotropin levels in an exome-wide association study.
| Autor: | Shi Y; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China., Miao BY; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China., Ai XX; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China; Reproductive Medicine Center, The Affiliated Shenzhen Maternity and Child Healthcare Hospital of the South Medical University, Shenzhen, Guangdong, China., Cao P; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China; Research School for Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands; Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden., Gao J; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China., Xu Y; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China., Yang Q; Peking Medriv Academy of Genetics and Reproduction, Peking, China., Fei J; Peking Medriv Academy of Genetics and Reproduction, Peking, China., Zhang Q; Peking Medriv Academy of Genetics and Reproduction, Peking, China., Mai QY; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China., Wen YX; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China., Qu YL; Department of Management Science and Engineering, Stanford University, Stanford, California., Zhou CQ; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China., Xu YW; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China. Electronic address: xuyanwen@mail.sysu.edu.cn. |
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| Jazyk: | angličtina |
| Zdroj: | Fertility and sterility [Fertil Steril] 2023 Sep; Vol. 120 (3 Pt 2), pp. 671-681. Date of Electronic Publication: 2023 Mar 29. |
| DOI: | 10.1016/j.fertnstert.2023.03.031 |
| Abstrakt: | Objective: To investigate whether common genetic polymorphisms are associated with gonadotropin levels after down-regulation with daily gonadotropin-releasing hormone agonist and whether the polymorphisms of candidate variants influence the ovarian response to exogenous gonadotropins. Design: Genetic association study. Setting: University-affiliated in vitro fertilization center. Patients: Subjects enrolled in an exploratory exome-wide association study (n = 862), a replication exome-wide association study (n = 86), and a classifier validation study (n = 148) were recruited from September 2016 to October 2018, September 2019 to September 2020, and January 2021 to December 2021, respectively. The included patients were aged ≤40 years and had a basal follicle-stimulating hormone (FSH) ≤12 IU/L. Interventions: All participants received a luteal phase down-regulation long protocol. Genome DNA was extracted from the peripheral blood leukocytes. For the exploratory and replication cohorts, exome sequencing was conducted on a HiSeq 2500 sequencing platform. The multiplex polymerase chain reaction amplification technique and next-generation sequencing also were performed in the exploratory and replication cohorts. For the samples of the validation cohort, Sanger sequencing was performed. Main Outcome Measures: The primary endpoint was the gonadotropin levels after down-regulation, and the secondary endpoints were hormone levels and follicle diameters during stimulation, the total dose of FSH, duration of FSH stimulation, number of oocytes retrieved, and clinical pregnancy rate. Results: In the exploratory cohort, we identified that FSHB rs6169 (P=2.71 × 10 -24 ) and its single-nucleotide polymorphisms in high linkage disequilibrium were associated with the down-regulated FSH level. The same locus was confirmed in the replication cohort. Women carrying the C allele of FSHB rs6169 exhibited higher average estradiol level during stimulation (P=6.82 × 10 -5 ), shorter duration of stimulation, and less amount of exogenous FSH (P Conclusion: The C allele of FSHB rs6169 is a susceptibility site for the relatively high level of FSH after down-regulation, which may be associated with increased ovarian FSH sensitivity. (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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