Wenqing Ma, Shuangmei Ye, Lifeng Tian, Min Liu, Rui Wang, Xuezhou Yang, Man Wang, Fangfang Fu, Wu Ren, Lei Dang, Tian Wang, Wenwen Wang, Shixuan Wang, Yan Sun, Yan Li
{"title":"LHCGR rs2293275基因型与中国女性卵巢衰老的关系：一项多中心人群研究","authors":"Wenqing Ma, Shuangmei Ye, Lifeng Tian, Min Liu, Rui Wang, Xuezhou Yang, Man Wang, Fangfang Fu, Wu Ren, Lei Dang, Tian Wang, Wenwen Wang, Shixuan Wang, Yan Sun, Yan Li","doi":"10.1186/s12958-025-01375-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the association between the LHCGR rs2293275 (N312S) genotype and ovarian aging phenotypes in Han Chinese women, focusing on diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI).</p><p><strong>Study design: </strong>This multicenter population-based study included 1,240 women aged 18-40 years diagnosed with DOR (n = 711) or POI (n = 529), alongside 72,846 ethnically and regionally matched controls from the Han Chinese Genomes Database (PGG.Han). Genotyping of rs2293275 was performed, and clinical data (menstrual history, hormonal profiles, maternal menopause age, and ART outcomes) were analyzed.</p><p><strong>Main results: </strong>The AA genotype frequency in the ovarian aging cohort (1.85%) was significantly higher than in the general Han population (0.62%, OR 3.04, 95% CI 1.99-4.64, p < 0.001). AA carriers exhibited earlier POI diagnosis (25.5 ± 6.4 vs. 32.0 ± 5.1 years in GG carriers, p < 0.001) and maternal menopause (41.6 ± 3.3 vs. 47.8 ± 4.1 years, p < 0.001). In controlled ovarian stimulation cycles, AA carriers demonstrated reduced ovarian sensitivity (OSI: 3.59 vs. 1.21 in GG, p = 0.019) despite comparable gonadotropin doses.</p><p><strong>Conclusions: </strong>The LHCGR rs2293275 AA genotype is strongly associated with accelerated ovarian aging in Han Chinese women, highlighting its potential as a biomarker for early identification of high-risk individuals. While these findings underscore genetic contributions to ovarian dysfunction, further mechanistic studies are needed to establish causality and optimize clinical translation.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov NCT05665010, registered on 2022-11-30.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"41"},"PeriodicalIF":4.2000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909885/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of LHCGR rs2293275 genotype with ovarian aging in Chinese women: a multicenter population-based study.\",\"authors\":\"Wenqing Ma, Shuangmei Ye, Lifeng Tian, Min Liu, Rui Wang, Xuezhou Yang, Man Wang, Fangfang Fu, Wu Ren, Lei Dang, Tian Wang, Wenwen Wang, Shixuan Wang, Yan Sun, Yan Li\",\"doi\":\"10.1186/s12958-025-01375-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To evaluate the association between the LHCGR rs2293275 (N312S) genotype and ovarian aging phenotypes in Han Chinese women, focusing on diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI).</p><p><strong>Study design: </strong>This multicenter population-based study included 1,240 women aged 18-40 years diagnosed with DOR (n = 711) or POI (n = 529), alongside 72,846 ethnically and regionally matched controls from the Han Chinese Genomes Database (PGG.Han). Genotyping of rs2293275 was performed, and clinical data (menstrual history, hormonal profiles, maternal menopause age, and ART outcomes) were analyzed.</p><p><strong>Main results: </strong>The AA genotype frequency in the ovarian aging cohort (1.85%) was significantly higher than in the general Han population (0.62%, OR 3.04, 95% CI 1.99-4.64, p < 0.001). AA carriers exhibited earlier POI diagnosis (25.5 ± 6.4 vs. 32.0 ± 5.1 years in GG carriers, p < 0.001) and maternal menopause (41.6 ± 3.3 vs. 47.8 ± 4.1 years, p < 0.001). In controlled ovarian stimulation cycles, AA carriers demonstrated reduced ovarian sensitivity (OSI: 3.59 vs. 1.21 in GG, p = 0.019) despite comparable gonadotropin doses.</p><p><strong>Conclusions: </strong>The LHCGR rs2293275 AA genotype is strongly associated with accelerated ovarian aging in Han Chinese women, highlighting its potential as a biomarker for early identification of high-risk individuals. While these findings underscore genetic contributions to ovarian dysfunction, further mechanistic studies are needed to establish causality and optimize clinical translation.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov NCT05665010, registered on 2022-11-30.</p>\",\"PeriodicalId\":21011,\"journal\":{\"name\":\"Reproductive Biology and Endocrinology\",\"volume\":\"23 1\",\"pages\":\"41\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909885/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive Biology and Endocrinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12958-025-01375-2\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive Biology and Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12958-025-01375-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Association of LHCGR rs2293275 genotype with ovarian aging in Chinese women: a multicenter population-based study.
Objective: To evaluate the association between the LHCGR rs2293275 (N312S) genotype and ovarian aging phenotypes in Han Chinese women, focusing on diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI).
Study design: This multicenter population-based study included 1,240 women aged 18-40 years diagnosed with DOR (n = 711) or POI (n = 529), alongside 72,846 ethnically and regionally matched controls from the Han Chinese Genomes Database (PGG.Han). Genotyping of rs2293275 was performed, and clinical data (menstrual history, hormonal profiles, maternal menopause age, and ART outcomes) were analyzed.
Main results: The AA genotype frequency in the ovarian aging cohort (1.85%) was significantly higher than in the general Han population (0.62%, OR 3.04, 95% CI 1.99-4.64, p < 0.001). AA carriers exhibited earlier POI diagnosis (25.5 ± 6.4 vs. 32.0 ± 5.1 years in GG carriers, p < 0.001) and maternal menopause (41.6 ± 3.3 vs. 47.8 ± 4.1 years, p < 0.001). In controlled ovarian stimulation cycles, AA carriers demonstrated reduced ovarian sensitivity (OSI: 3.59 vs. 1.21 in GG, p = 0.019) despite comparable gonadotropin doses.
Conclusions: The LHCGR rs2293275 AA genotype is strongly associated with accelerated ovarian aging in Han Chinese women, highlighting its potential as a biomarker for early identification of high-risk individuals. While these findings underscore genetic contributions to ovarian dysfunction, further mechanistic studies are needed to establish causality and optimize clinical translation.
Trial registration number: ClinicalTrials.gov NCT05665010, registered on 2022-11-30.
期刊介绍：
Reproductive Biology and Endocrinology publishes and disseminates high-quality results from excellent research in the reproductive sciences.
The journal publishes on topics covering gametogenesis, fertilization, early embryonic development, embryo-uterus interaction, reproductive development, pregnancy, uterine biology, endocrinology of reproduction, control of reproduction, reproductive immunology, neuroendocrinology, and veterinary and human reproductive medicine, including all vertebrate species.
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