Wanqin Feng1, Yan Zhang2, Yuan Pan3, Yi Zhang3, Minjuan Liu1,4, Yuxin Huang5, Yuanling Xiao5, Wenyu Mo1, Junjie Jiao6, Xiaoyang Wang1, Dan Tian5, Lixia Yang7, Ying Ma8. 1. Department of Gynecology, Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, No.253, Gongye Middle Avenue, Haizhu District, 510280, Guangzhou, Guangdong, China. 2. Clinical Research Center, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China. 3. Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China. 4. Department of Obstetrics and Gynecology, Dongguan People's Hospital, 523000, Dongguan, China. 5. Department of Obstetrics, Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China. 6. Department of Fetal Medicine and Prenatal Diagnosis, Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China. 7. Department of Emergency, Zhujiang Hospital, Southern Medical University, 510280, Guangzhou, China. 8. Department of Gynecology, Obstetrics and Gynecology Center, Zhujiang Hospital, Southern Medical University, No.253, Gongye Middle Avenue, Haizhu District, 510280, Guangzhou, Guangdong, China. mayingwuzhuoyi@126.com.
Abstract
BACKGROUND: The etiology between homocysteine and polycystic ovary syndrome (PCOS) is unclear. In humans, the level of homocysteine is mainly affected by two enzymes: methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR). While the activity of these two enzymes is mainly affected by three missense mutations, namely C677T (MTHFR), A1298C (MTHFR), and A66G (MTRR). This study aims to examine the association between the three missense mutations and PCOS and investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. METHODS: A case-control study was designed, comprising 150 people with PCOS and 300 controls. Logistic regression analysis was used to assess the association between the three missense mutations and PCOS. Linear regression analysis was used to assess the association between the three missense mutations and the homocysteine level. Mediation analysis was used to investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. RESULTS: Following adjustments and multiple rounds of testing, MTHFR A1298C was found to be significantly associated with PCOS in a dose-dependent manner (compared to AA, OR = 2.142 for AC & OR = 3.755 for CC; P < 0.001). MTRR A66G was nominally associated with PCOS. Mutations in MTHFR A1298C and MTRR A66G were significantly associated with the homocysteine level. Mediation analysis suggested the effect of MTHFR A1298C on PCOS was mediated by homocysteine. CONCLUSIONS: MTHFR A1298C and MTRR A66G were associated with PCOS, and MTHFR A1298C might affect the risk of PCOS by influencing the homocysteine level.
BACKGROUND: The etiology between homocysteine and polycystic ovary syndrome (PCOS) is unclear. In humans, the level of homocysteine is mainly affected by two enzymes: methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR). While the activity of these two enzymes is mainly affected by three missense mutations, namely C677T (MTHFR), A1298C (MTHFR), and A66G (MTRR). This study aims to examine the association between the three missense mutations and PCOS and investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. METHODS: A case-control study was designed, comprising 150 people with PCOS and 300 controls. Logistic regression analysis was used to assess the association between the three missense mutations and PCOS. Linear regression analysis was used to assess the association between the three missense mutations and the homocysteine level. Mediation analysis was used to investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. RESULTS: Following adjustments and multiple rounds of testing, MTHFRA1298C was found to be significantly associated with PCOS in a dose-dependent manner (compared to AA, OR = 2.142 for AC & OR = 3.755 for CC; P < 0.001). MTRRA66G was nominally associated with PCOS. Mutations in MTHFRA1298C and MTRRA66G were significantly associated with the homocysteine level. Mediation analysis suggested the effect of MTHFRA1298C on PCOS was mediated by homocysteine. CONCLUSIONS:MTHFRA1298C and MTRRA66G were associated with PCOS, and MTHFRA1298C might affect the risk of PCOS by influencing the homocysteine level.
Authors: Daniel A Dumesic; Sharon E Oberfield; Elisabet Stener-Victorin; John C Marshall; Joop S Laven; Richard S Legro Journal: Endocr Rev Date: 2015-10 Impact factor: 19.871
Authors: Richard S Legro; Silva A Arslanian; David A Ehrmann; Kathleen M Hoeger; M Hassan Murad; Renato Pasquali; Corrine K Welt Journal: J Clin Endocrinol Metab Date: 2013-10-22 Impact factor: 5.958
Authors: Felix Day; Tugce Karaderi; Michelle R Jones; Cindy Meun; Chunyan He; Alex Drong; Peter Kraft; Nan Lin; Hongyan Huang; Linda Broer; Reedik Magi; Richa Saxena; Triin Laisk; Margrit Urbanek; M Geoffrey Hayes; Gudmar Thorleifsson; Juan Fernandez-Tajes; Anubha Mahajan; Benjamin H Mullin; Bronwyn G A Stuckey; Timothy D Spector; Scott G Wilson; Mark O Goodarzi; Lea Davis; Barbara Obermayer-Pietsch; André G Uitterlinden; Verneri Anttila; Benjamin M Neale; Marjo-Riitta Jarvelin; Bart Fauser; Irina Kowalska; Jenny A Visser; Marianne Andersen; Ken Ong; Elisabet Stener-Victorin; David Ehrmann; Richard S Legro; Andres Salumets; Mark I McCarthy; Laure Morin-Papunen; Unnur Thorsteinsdottir; Kari Stefansson; Unnur Styrkarsdottir; John R B Perry; Andrea Dunaif; Joop Laven; Steve Franks; Cecilia M Lindgren; Corrine K Welt Journal: PLoS Genet Date: 2018-12-19 Impact factor: 6.020